Kevin_Struhl

Kevin Struhl

Kevin Struhl

American biochemist

Kevin Struhl (born September 2, 1952) is an American molecular biologist and the David Wesley Gaiser Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School.[1]  Struhl is primarily known for his work on transcriptional regulatory mechanisms in yeast using molecular, genetic, biochemical, and genomic approaches.[2]  More recently, he has used related approaches to study transcriptional regulatory circuits involved in cellular transformation and the formation of cancer stem cells.

Quick Facts Born, Nationality ...

Early life and education

Kevin Struhl was born on September 2, 1952, in Brooklyn, New York. His father, Joseph Struhl (1921-2008), was an entrepreneur who put up some of the first indoor tennis courts.[3][4] His mother, Harriet Schachter Struhl (1927-) was a psychologist. He has 3 younger brothers, Gary (1954-), a developmental geneticist at Columbia Medical School, Clifford (1956-) who took over the family business, and Steven (1958-) an orthopedic surgeon.[5] The Struhl family moved to Great Neck, NY in 1956, where Struhl graduated from Great Neck South high school in 1970. Struhl and his father were once ranked #3 in father-son tennis in the Eastern section of the United States Tennis Association.  Struhl completed his S.B and S.M. in biology in 1974 with Boris Magasanik from the Massachusetts Institute of Technology. He obtained his Ph.D. in 1979 with Ronald W. Davis at Stanford Medical School and then spent two years as a postdoctoral fellow with Sydney Brenner at the Laboratory of Molecular Biology at the Medical Research Council in Cambridge, UK.

Career and Research

Recombinant DNA technology, yeast molecular biology, and reverse genetics

As a graduate student, Struhl cloned and functionally expressed the first eukaryotic protein-coding gene in E.coli, a landmark in recombinant DNA technology.[6][7] Cloned yeast genes were essential for Gerald Fink to develop transformation methods that Struhl used to co-discover DNA replication origins[8][9] and to create the first vectors for molecular genetic manipulations in yeast.[8] Struhl was among the first to use “reverse genetic” analysis; i.e., making mutations in cloned genes, introducing the mutated derivatives back into cells, and assessing the resulting phenotypes.[10]

Structure and function of eukaryotic promoters: the yeast his3 paradigm

Using “reverse genetics” to study gene regulation in vivo, Struhl generated the first eukaryotic promoter mutants and performed a detailed analysis of the his3 gene. This resulted in early descriptions of all the basic types of gene-regulatory elements: upstream elements that act a distance from the promoter;[11][10] regulatory sites that activate gene expression in specific conditions;[12] poly(dA:dT) sequences;[13] functionally distinct TATA elements;[14][15] initiator elements;[16] repression sequences that act upstream of and at a distance from promoters.[17]

Structure and function of a transcriptional activator, the yeast Gcn4 paradigm

Struhl invented “reverse biochemistry”, the use of in vitro synthesized proteins to identify DNA-binding transcription factors and study protein-DNA interactions.[18] In one of the first examples of a eukaryotic sequence-specific binding protein, he discovered that Gcn4 coordinately activates many genes involved in amino acid biosynthesis by direct binding to bound target sites in their promoters.[18] He developed the first “random selection” method for DNA target sites (and other genetic elements) from random-sequence oligonucleotides.[19] He showed that Gcn4 binds as a dimer[20] via its leucine zipper,[21] described how it recognizes target sites at atomic resolution,[22] and showed that the Gcn4 binding surface folds when bound to its target site, the first example of an “induced fit” model for DNA binding.[23] Detailed genetic dissection led to the discovery of short acidic activation domains required for transcription that are functionally autonomous and can be encoded by different sequences.[24][25] Lastly, Struhl showed that the Jun oncogene encodes a Gcn4 homolog that binds the same sequences[26] and activates transcription in yeast cells.[27] Jun was the first example of an oncogene that encodes a transcription factor.

Transcriptional regulatory mechanisms

Using T7 RNA polymerase in yeast cells, Struhl demonstrated distinct chromatin-accessibility and protein-protein interaction mechanisms for transcriptional activation.[28] Novel genetic approaches - altered-specificity mutants,[29] protein fusions for artificial recruitment[30][31] - along with chromatin immunoprecipitation (ChIP), demonstrated that transcriptional regulation in yeast occurs primarily at the level of recruitment of the RNA polymerase II transcription machinery.[32] Struhl showed that the TATA-binding protein is required for transcription by all 3 nuclear RNA polymerases[33] and defined a surface required specifically for transcription by RNA polymerase III.[34] Together with Tom Gingeras, he used tiled microarrays to generate the first unbiased, genome-scale analysis of transcription factor binding in mammalian cells, leading to the discovery of far more transcription binding sites in vivo than predicted, including many that control non-coding RNAs.[35][36]  His contributions in diverse areas of transcriptional regulation include mechanistic roles of general factors for transcriptional initiation,[37][38][39][40] promoter directionality,[41] high level of transcriptional noise due to infidelity of Pol II initiation,[42] role of TAFs[43][44][45] and Mediator[46][47] in transcriptional activation, coordinate regulation of ribosomal protein genes in response to growth and stress signals,[48][49] repression by the Cyc8-Tup co-repressor complex that controls numerous stress pathways,[50][51] the response to osmotic stress[52] including the discovery of a pre-transcriptional response,[53] transcriptional elongation,[54][55] 3’ end formation,[55][56] and mRNA stability.[57][58] Lastly, Struhl was among the first to use ChIP to analyze transcription in E. coli, showing that the transition between initiation and elongation is highly variable and often rate-limiting[59] and uncovering extensive functional overlap between sigma factors.[60]

Role of chromatin in transcription and DNA replication

Struhl’s work on the role of chromatin in transcriptional regulation include initial descriptions of 1) a DNA sequence, poly(dA:dT), that activates transcription via its intrinsic effect on nucleosome stability,[61][62] 2) mechanistic principles for how the nucleosome positioning pattern occurs in vivo,[63][64] 3) transcriptional repression via targeted recruitment of a histone deacetylase,[65][66] 4) molecular memory of recent transcriptional activity via targeted histone methylation via recruitment by elongating Pol II,[67] 5) dynamic eviction and re-association of histones during transcriptional elongation,[68] and 6) methylation of lysine 79 within the histone H3 core[69] and a model for position-effect variegation.[70] With respect to DNA replication, Struhl demonstrated that a histone acetylase (HBO1) is both a transcriptional co-activator and a co-activator for the Cdt1 replication licensing factor[71][72] that coordinates the transcriptional and DNA replication response to non-genotoxic stress.[73] In addition, he showed that the DNA origin replication complex (ORC) selectively binds regions with a specific chromatin pattern, and that the location of ORC binding sites plays a major role in DNA replication timing.[74]

An epigenetic switch linking inflammation to cancer

Struhl discovered an epigenetic switch from non-transformed to transformed cells, a new type of step in cancer progression distinct from mutation or DNA methylation.[75] This epigenetic switch is mediated by a positive inflammatory feedback loop that involves the joint role of the NF-kB, STAT3, AP-1, and TEAD transcription factors along with YAP/TAZ co-activators as well as Let7 and other microRNAs.[76][77][78] He also uncovered a dynamic equilibrium between cancer stem cells and non-stem cancer cells mediated by interleukin 6[79] and defined the transcriptional circuit mediating the biphasic switch between these physiological states.[80][81]

Anti-cancer and anti-inflammatory properties of metformin

Struhl showed that metformin, the first-line drug for treating type 2 diabetes, selectively kills cancer stem cells and acts together with chemotherapy to inhibit tumor progression and prolong remission.[82][83] Metformin exerts its effects on cellular transformation and cancer stem cell growth via its inhibitory effect on the inflammatory pathway.[84]

Awards

References

  1. [1]
    Chandler, Courtney (2022-12-02). "'Independent agents' no more". American Society for Biochemistry and Molecular Biology.
  2. [2]
    Struhl, Kevin (1995). "Yeast Transcriptional Regulatory Mechanisms". Annual Review of Genetics. 29: 651–674. doi:10.1146/annurev.ge.29.120195.003251. PMID 8825489.
  3. [3]
    Horn, Houston (1965-03-08). "As Long As There's A Place To Go, Let It Snow". Sports Illustrated.
  4. [4]
    Friedman, Charles (1964-11-22). "$400,000 Indoor Tennis Center With 4 Clay Courts Opens Here" (PDF). The New York Times.
  5. [5]
    "Dr. Steven Struhl NYC Orthopedic Surgeon". Shoulders & Knees Steven Struhl MD.
  6. [6]
    Struhl, K; Davis, RW (1977-12-01). "Production of a functional eukaryotic enzyme in Escherichia coli: cloning and expression of the yeast structural gene for imidazole-glycerolphosphate dehydratase (his3)". PNAS. 74 (12): 5255–5259. Bibcode:1977PNAS...74.5255S. doi:10.1073/pnas.74.12.5255. PMC 431671. PMID 341150.
  7. [7]
    Struhl, K; Cameron, JR; Davis, RW (1976-05-01). "Functional genetic expression of eukaryotic DNA in Escherichia coli". PNAS. 73 (5): 1471–1475. Bibcode:1976PNAS...73.1471S. doi:10.1073/pnas.73.5.1471. PMC 430318. PMID 775490.
  8. [8]
    Struhl, K; Stinchcomb, DT; Scherer, S; Davis, RW (1979-03-01). "High-frequency transformation of yeast: autonomous replication of hybrid DNA molecules". PNAS. 76 (3): 1035–1039. Bibcode:1979PNAS...76.1035S. doi:10.1073/pnas.76.3.1035. PMC 383183. PMID 375221.
  9. [9]
    Stinchcomb, DT; Struhl, K; Davis, RW (1979-11-01). "Isolation and characterization of a yeast chromosomal replicator". Nature. 282 (5734): 39–43. Bibcode:1979Natur.282...39S. doi:10.1038/282039a0. PMID 388229. S2CID 4326901.
  10. [10]
    Struhl, Kevin (1979). "The yeast his3 gene". Biochemistry.
  11. [11]
    Struhl, Kevin (1981-07-01). "Deletion mapping a eukaryotic promoter". PNAS. 78 (7): 4461–4465. Bibcode:1981PNAS...78.4461S. doi:10.1073/pnas.78.7.4461. PMC 319811. PMID 7027262.
  12. [12]
    Struhl, Kevin (1982-11-18). "Regulatory sites for his3 expression in yeast". Nature. 300 (5889): 285–286. doi:10.1038/300284a0. PMID 6755264. S2CID 4308484.
  13. [13]
    Struhl, Kevin (1985-12-01). "Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast". PNAS. 82 (24): 8419–8423. Bibcode:1985PNAS...82.8419S. doi:10.1073/pnas.82.24.8419. PMC 390927. PMID 3909145.
  14. [14]
    Chen, W; Struhl, K (1988-04-01). "Saturation mutagenesis of a yeast his3 TATA element: genetic evidence for a specific TATA-binding protein". PNAS. 85 (8): 2691–2695. Bibcode:1988PNAS...85.2691C. doi:10.1073/pnas.85.8.2691. PMC 280064. PMID 3282236.
  15. [15]
    Struhl, Kevin (1986-05-29). "Constitutive and inducible Saccharomyces cerevisiae promoters: evidence for two distinct molecular mechanisms". Molecular and Cellular Biology. 6 (11): 3847–3853. doi:10.1128/mcb.6.11.3847-3853.1986. PMC 367147. PMID 3540601.
  16. [16]
    Chen, W; Struhl, K (1985-12-01). "Yeast mRNA initiation sites are determined primarily by specific sequences, not by the distance from the TATA element". The EMBO Journal. 4 (12): 3273–3280. doi:10.1002/j.1460-2075.1985.tb04077.x. PMC 554654. PMID 3912167.
  17. [17]
    Struhl, Kevin (1985-10-01). "Negative control at a distance mediates catabolite repression in yeast". Nature. 317 (6040): 822–824. Bibcode:1985Natur.317..822S. doi:10.1038/317822a0. PMID 3903516. S2CID 2404872.
  18. [18]
    Hope, IA; Struhl, K (November 1988). "GCN4 protein, synthesized in vitro, binds to HIS3 regulatory sequences: implications for the general control of amino acid biosynthetic genes in yeast". Cell. 43 (1): 177–188. doi:10.1016/0092-8674(85)90022-4. PMID 3907851. S2CID 22627291.
  19. [19]
    Oliphant, AR; Brandl, CJ; Struhl, K (1989-07-01). "Defining sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: Analysis of the yeast GCN4 protein". Molecular and Cellular Biology. 9 (7): 2944–2949. doi:10.1128/mcb.9.7.2944-2949.1989. PMC 362762. PMID 2674675.
  20. [20]
    Hope, IA; Struhl, K (1987-09-01). "GCN4, a eukaryotic transcriptional activator protein, binds as a dimer to target DNA". The EMBO Journal. 6 (9): 2781–2784. doi:10.1002/j.1460-2075.1987.tb02573.x. PMC 553703. PMID 3678204.
  21. [21]
    Sellers, JW; Struhl, K (1989-09-07). "Changing fos oncoprotein to a DNA-binding protein with GCN4 dimerization specificity by swapping "leucine zippers"". Nature. 341 (6237): 74–76. doi:10.1038/341074a0. PMID 2505087. S2CID 4253004.
  22. [22]
    Ellenberger, Thomas E; Brandl, Christopher J; Struhl, Kevin; Harrison, Stephen C (1992-12-24). "The GCN4 basic-region-leucine zipper binds DNA as a dimer of uninterrupted a-helices: crystal structure of the protein-DNA complex". Cell. 71 (7): 1223–1237. doi:10.1016/S0092-8674(05)80070-4. PMID 1473154. S2CID 13548424.
  23. [23]
    Weiss, Michael A; Ellenberger, Thomas; Wobbe, C Richard; Lee, Jonathan P; Harrison, Stephen C; Struhl, Kevin (1990). "Folding transition in the DNA-binding domain of GCN4 on specific binding to DNA". Nature. 347 (6293): 575–578. Bibcode:1990Natur.347..575W. doi:10.1038/347575a0. PMID 2145515. S2CID 4366430.
  24. [24]
    Hope, IA; Struhl, K (1986-09-12). "Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast". Cell. 46 (6): 885–894. doi:10.1016/0092-8674(86)90070-X. PMID 3530496. S2CID 40730692.
  25. [25]
    Hope, IA; Mahadevan, S; Struhl, K (1988-06-16). "Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein". Nature. 333 (6174): 635–640. Bibcode:1988Natur.333..635H. doi:10.1038/333635a0. PMID 3287180. S2CID 2635634.
  26. [26]
    Struhl, Kevin (1987-09-11). "The DNA-binding domains of the jun oncoprotein and the yeast GCN4 transcriptional activator are functionally homologous". Cell. 50 (6): 841–846. doi:10.1016/0092-8674(87)90511-3. PMID 3040261. S2CID 29588878.
  27. [27]
    Struhl, Kevin (1988-04-14). "The JUN oncoprotein, a vertebrate transcription factor, activates transcription in yeast". Nature. 332 (6165): 649–650. Bibcode:1988Natur.332..649S. doi:10.1038/332649a0. PMID 3128739. S2CID 4350206.
  28. [28]
    Chen, W; Tabor, S; Struhl, K (1987-09-25). "Distinguishing between mechanisms of eukaryotic transcriptional activation with bacteriophage T7 RNA polymerase". Cell. 266 (5183): 280–282. doi:10.1126/science.7939664. PMID 7939664.
  29. [29]
    Klein, C; Struhl, K (1994-10-19). "Increased recruitment of TATA-binding protein to the promoter by transcriptional activation domains in vivo". Science. 266 (5183): 280–282. doi:10.1126/science.7939664. PMID 7939664.
  30. [30]
    Keaveney, M; Struhl, K (May 1998). "Activator-mediated recruitment of the RNA polymerase II machinery is the predominant mechanism for transcriptional activation in yeast". Molecular Cell. 1 (6): 917–924. doi:10.1016/S1097-2765(00)80091-X. PMID 9660975.
  31. [31]
    Chatterjee, S; Struhl, K (1995-04-27). "Connecting a promoter-bound protein to TBP bypasses the need for a transcriptional activation domain". Nature. 374 (6525): 820–822. doi:10.1038/374820a0. PMID 7723828. S2CID 4325887.
  32. [32]
    Kuras, L; Struhl, K (1999-06-10). "Binding of TBP to promoters in vivo is stimulated by activators and requires Pol II holoenzyme". Nature. 399 (6736): 609–613. doi:10.1038/21239. PMID 10376605. S2CID 204993837.
  33. [33]
    Cormack, BP; Struhl, K (1992-05-15). "The TATA-binding protein is required for transcription by all three nuclear RNA polymerases in yeast cells". Cell. 69 (4): 685–696. doi:10.1016/0092-8674(92)90232-2. PMID 1586947. S2CID 7419671.
  34. [34]
    Cormack, BP; Struhl, K (1993-10-08). "Regional codon randomization: defining a TATA-binding protein surface required for RNA polymerase III transcription". Science. 262 (5131): 244–248. doi:10.1126/science.8211143. PMID 8211143.
  35. [35]
    Cawley, S.; et al. (2004-02-20). "Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of non-coding RNAs". Cell. 116 (4): 499–509. doi:10.1016/S0092-8674(04)00127-8. PMID 14980218. S2CID 7793221.
  36. [36]
    Yang, Annie; Zhu, Zhou; Kapranov, Philipp; McKeon, Frank; Church, George M; Gingeras, Thomas R; Struhl, Kevin (2006-11-17). "Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells". Molecular Cell. 24 (4): 593–602. doi:10.1016/j.molcel.2006.10.018. PMID 17188034.
  37. [37]
    Stargell, LA; Struhl, K (1995-07-07). "The TBP-TFIIA interaction in the response to acidic activators in vivo". Science. 269 (5220): 75–78. doi:10.1126/science.7604282. PMID 7604282.
  38. [38]
    Lee, M; Struhl, K (1995-07-11). "Mutations on the DNA-binding surface of TATA-binding protein can specifically impair the response to acidic activators in vivo". Molecular and Cellular Biology. 15 (10): 5461–5469. doi:10.1128/MCB.15.10.5461. PMC 230796. PMID 7565697.
  39. [39]
    Petrenko, Natalia; Yi, Jin; Dong, Liguo; Wong, Koon Ho; Struhl, Kevin (2019-01-25). "Requirements for RNA polymerase II preinitiation complex formation in vivo". eLife. 8. doi:10.7554/eLife.43654.023. PMC 6366898. PMID 30681409.
  40. [40]
    Wong, Koon Ho; Yi, Jin; Struhl, Kevin (2014-05-22). "TFIIH phosphorylation of the Pol II CTD stimulates Mediator dissociation from the preinitiation complex and promoter escape". Molecular Cell. 54 (4): 601–612. doi:10.1016/j.molcel.2014.03.024. PMC 4035452. PMID 24746699.
  41. [41]
    Yi, Jin; Eser, Umut; Struhl, Kevin; Churchman, L Stirling (2017-08-24). "The ground state and evolution of promoter regions directionality". Cell. 170 (5): 889–898.e10. doi:10.1016/j.cell.2017.07.006. PMC 5576552. PMID 28803729.
  42. [42]
    Struhl, Kevin (February 2007). "Transcriptional noise and the fidelity of initiation by RNA polymerase II". Nature Structural & Molecular Biology. 14 (2): 103–105. doi:10.1038/nsmb0207-103. PMID 17277804. S2CID 29398526.
  43. [43]
    Moqtaderi, Zarmik; Bai, Yu; Poon, David; Weil, P Anthony; Struhl, Kevin (1996-09-12). "TBP-associated factors are not generally required for transcriptional activation in yeast". Nature. 383 (6596): 188–191. doi:10.1038/383188a0. PMID 8774887. S2CID 4351320.
  44. [44]
    Kuras, Laurent; Kosa, Peter; Mencia, Mario; Struhl, Kevin (2000-05-19). "TAF-containing and TAF-independent forms of transcriptionally active TBP in vivo". Science. 288 (5469): 1244–1248. doi:10.1126/science.288.5469.1244. PMID 10818000.
  45. [45]
    Mencia, Mario; Moqtaderi, Zarmik; Geisberg, Joseph V; Kuras, Laurent; Struhl, Kevin (April 2002). "Activator-specific recruitment of TFIID and regulation of ribosomal protein genes in yeast". Molecular Cell. 9 (4): 823–833. doi:10.1016/S1097-2765(02)00490-2. PMID 11983173.
  46. [46]
    Fan, Xiaochun; Chou, Danny M; Struhl, Kevin (2006-01-22). "Activator-specific recruitment of Mediator in vivo". Nature Structural & Molecular Biology. 13 (2): 117–120. doi:10.1038/nsmb1049. PMID 16429153. S2CID 20626638.
  47. [47]
    Petrenko, Natalia; Jin, Yi; Wong, Koon Ho; Struhl, Kevin (2016-11-03). "Mediator Undergoes a Compositional Change during Transcriptional Activation". Molecular Cell. 64 (3): 443–454. doi:10.1016/j.molcel.2016.09.015. PMC 5096951. PMID 27773675.
  48. [48]
    Klein, C; Struhl, K (March 1994). "Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity". Molecular and Cellular Biology. 14 (3): 1920–1928. doi:10.1128/mcb.14.3.1920-1928.1994. PMC 358550. PMID 8114723.
  49. [49]
    Wade, Joseph T; Hall, Daniel B; Struhl, Kevin (2004-12-23). "The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes". Nature. 432 (7020): 1054–1058. doi:10.1038/nature03175. PMID 15616568. S2CID 4334147.
  50. [50]
    Tzamarias, D; Struhl, K (1994-06-30). "Functional dissection of the yeast Cyc8-Tup1 transcriptional corepressor complex". Nature. 369 (6483): 758–761. doi:10.1038/369758a0. PMID 8008070. S2CID 4304771.
  51. [51]
    Wong, Koon Ho; Struhl, Kevin (2011-12-01). "The Cyc8-Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein". Genes & Development. 25 (23): 2525–2539. doi:10.1101/gad.179275.111. PMC 3243062. PMID 22156212.
  52. [52]
    Proft, M; Struhl, K (June 2002). "Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an activator that recruits SAGA and SWI/SNF in response to osmotic stress". Molecular Cell. 9 (6): 1307–1317. doi:10.1016/S1097-2765(02)00557-9. PMID 12086627.
  53. [53]
    Proft, M; Struhl, K (2004-08-06). "A MAP kinase-mediated stress relief response that precedes and regulates the timing of transcriptional induction". Cell. 118 (3): 351–361. doi:10.1016/j.cell.2004.07.016. PMID 15294160. S2CID 2022911.
  54. [54]
    Mason, Paul B; Struhl, Kevin (2005-03-18). "Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo". Molecular Cell. 17 (6): 831–840. doi:10.1016/j.molcel.2005.02.017. PMID 15780939.
  55. [55]
    Geisberg, Joseph V; Moqtaderi, Zarmik; Struhl, Kevin (2020-08-26). "The transcriptional elongation rate regulates alternative polyadenylation in yeast". eLife. 9. doi:10.7554/eLife.59810.sa2. PMC 7532003. PMID 32845240.
  56. [56]
    Geisberg, Joseph V; Moqtaderi, Zarmik; Fong, Nova; Erickson, Benjamin; Bentley, David L; Struhl, Kevin (2022-11-24). "Nucleotide-level linkage of transcriptional elongation and polyadenylation". eLife. 11. doi:10.7554/eLife.83153.sa2. PMC 9721619. PMID 36421680.
  57. [57]
    Geisberg, Joseph V; Moqtaderi, Zarmik; Fan, Xiaochun; Ozsolak, Fatih; Struhl, Kevin (2014-02-13). "Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast". Cell. 156 (4): 812–824. doi:10.1016/j.cell.2013.12.026. PMC 3939777. PMID 24529382.
  58. [58]
    Moqtaderi, Zarmik; Geisberg, Joseph V; Struhl, Kevin (October 2018). "Extensive structural differences of closely related 3' mRNA isoforms: links to Pab1 binding and mRNA stability". Molecular Cell. 72 (5): 849–861.e6. doi:10.1016/j.molcel.2018.08.044. PMC 6289678. PMID 30318446.
  59. [59]
    Reppas, Nikos B; Wade, Joseph T; Church, George M; Struhl, Kevin (2006-12-08). "The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate-limiting". Molecular Cell. 24 (5): 747–757. doi:10.1016/j.molcel.2006.10.030. PMID 17157257.
  60. [60]
    Wade, Joseph T; Roa, Daniel Castro; Grainger, David C; Hurd, Douglas; Busby, Stephen JW; Struhl, Kevin; Nudler, Evgeny (2006-08-06). "Extensive functional overlap between σ factors in Escherichia coli". Nature Structural & Molecular Biology. 13 (9): 806–814. doi:10.1038/nsmb1130. PMID 16892065. S2CID 19816595.
  61. [61]
    Iyer, V; Struhl, K (June 1995). "Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic structure". The EMBO Journal. 14 (11): 2570–2579. doi:10.1002/j.1460-2075.1995.tb07255.x. PMC 398371. PMID 7781610.
  62. [62]
    Sekinger, Edward A; Moqtaderi, Zarmik; Struhl, Kevin (2005-06-10). "Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast". Molecular Cell. 18 (6): 735–748. doi:10.1016/j.molcel.2005.05.003. PMID 15949447.
  63. [63]
    Zhang, Yong; Moqtaderi, Zarmik; Rattner, Barbara P; Euskirchen, Ghia; Snyder, Michael; Kadonaga, James T; Liu, X Shirley; Struhl, Kevin (2009-07-20). "Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo". Nature Structural & Molecular Biology. 16 (8): 847–852. doi:10.1038/nsmb.1636. PMC 2823114. PMID 19620965. S2CID 11805076.
  64. [64]
    Hughes, Amanda L; Jin, Yi; Rando, Oliver J; Struhl, Kevin (2012-10-12). "A Functional Evolutionary Approach to Identify Determinants of Nucleosome Positioning: A Unifying Model for Establishing the Genome-wide Pattern". Molecular Cell. 48 (1): 5–15. doi:10.1016/j.molcel.2012.07.003. PMC 3472102. PMID 22885008.
  65. [65]
    Kadosh, David; Struhl, Kevin (1997-05-02). "Repression by Ume6 Involves Recruitment of a Complex Containing Sin3 Corepressor and Rpd3 Histone Deacetylase to Target Promoters". Cell. 89 (3): 365–371. doi:10.1016/S0092-8674(00)80217-2. PMID 9150136. S2CID 15115179.
  66. [66]
    Kadosh, David; Struhl, Kevin (September 1998). "Targeted Recruitment of the Sin3-Rpd3 Histone Deacetylase Complex Generates a Highly Localized Domain of Repressed Chromatin In Vivo". Molecular and Cellular Biology. 18 (9): 5121–5127. doi:10.1128/MCB.18.9.5121. PMC 109097. PMID 9710596.
  67. [67]
    Ng, Huck Hui; Robert, Francois; Young, Richard A; Struhl, Kevin (March 2003). "Targeted Recruitment of Set1 Histone Methylase by Elongating Pol II Provides a Localized Mark and Memory of Recent Transcriptional Activity". Molecular Cell. 11 (3): 709–719. doi:10.1016/S1097-2765(03)00092-3. PMID 12667453.
  68. [68]
    Schwabish, Marc A; Struhl, Kevin (December 2004). "Evidence for Eviction and Rapid Deposition of Histones upon Transcriptional Elongation by RNA Polymerase II". Molecular and Cellular Biology. 24 (23): 10111–10117. doi:10.1128/MCB.24.23.10111-10117.2004. PMC 529037. PMID 15542822.
  69. [69]
    Ng, Huck Hui; Feng, Qin; Wang, Hengbin; Erdjument-Bromage, Hediye; Tempst, Paul; Zhang, Yi; Struhl, Kevin (2002). "Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association". Genes & Development. 16 (12): 1518–1527. doi:10.1101/gad.1001502. PMC 186335. PMID 12080090.
  70. [70]
    Ng, Huck Hui; Ciccone, David N; Morshead, Katrina B; Oettinger, Marjorie A; Struhl, Kevin (2003-02-06). "Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation". PNAS. 100 (4): 1820–1825. doi:10.1073/pnas.0437846100. PMC 149917. PMID 12574507.
  71. [71]
    Miotto, Benoit; Struhl, Kevin (2008). "HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1". Genes & Development. 22 (19): 2633–2638. doi:10.1101/gad.1674108. PMC 2559906. PMID 18832067.
  72. [72]
    Miotto, Benoit; Struhl, Kevin (2010-01-15). "HBO1 Histone Acetylase Activity Is Essential for DNA Replication Licensing and Inhibited by Geminin". Molecular Cell. 37 (1): 57–66. doi:10.1016/j.molcel.2009.12.012. PMC 2818871. PMID 20129055.
  73. [73]
    Miotto, Benoit; Struhl, Kevin (2011-10-07). "JNK1 Phosphorylation of Cdt1 Inhibits Recruitment of HBO1 Histone Acetylase and Blocks Replication Licensing in Response to Stress". Molecular Cell. 44 (1): 62–71. doi:10.1016/j.molcel.2011.06.021. PMC 3190045. PMID 21856198.
  74. [74]
    Miotto, Benoit; Ji, Zhe; Struhl, Kevin (2016-06-14). "Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers". PNAS. 113 (33): 4810–4819. doi:10.1073/pnas.1609060113. PMC 4995967. PMID 27436900.
  75. [75]
    Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin (2009-11-13). "An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation". Cell. 139 (4): 693–706. doi:10.1016/j.cell.2009.10.014. PMC 2783826. PMID 19878981.
  76. [76]
    He, Lizhi; Pratt, Henry; Gao, Mingshi; Wei, Fengxiang; Weng, Zhiping; Struhl, Kevin (2021-08-21). "YAP and TAZ are transcriptional co-activators of AP-1 proteins and STAT3 during breast cellular transformation". eLife. 10. doi:10.7554/eLife.67312. PMC 8463077. PMID 34463254.
  77. [77]
    Iliopoulos, Dimitrios; Jaeger, Savina A; Hirsch, Heather A; Bulyk, Martha L; Struhl, Kevin (2010-08-27). "STAT3 Activation of miR-21 and miR-181b-1 via PTEN and CYLD Are Part of the Epigenetic Switch Linking Inflammation to Cancer". Molecular Cell. 39 (4): 493–506. doi:10.1016/j.molcel.2010.07.023. PMC 2929389. PMID 20797623.
  78. [78]
    Ji, Zhe; He, Lizhi; Regev, Aviv; Struhl, Kevin (2019-03-25). "Inflammatory regulatory network mediated by the joint action of NF-kB, STAT3, and AP-1 factors is involved in many human cancers". PNAS. 116 (19): 9453–9462. doi:10.1073/pnas.1821068116. PMC 6511065. PMID 30910960.
  79. [79]
    Iliopoulos, Dimitrios; Hirsch, Heather A; Wang, Guannan; Struhl, Kevin (2011-01-10). "Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion". PNAS. 108 (4): 1397–1402. doi:10.1073/pnas.1018898108. PMC 3029760. PMID 21220315.
  80. [80]
    Iliopoulos, Dimitrios; Lindahl-Allen, Marianne; Polytarchou, Christos; Hirsch, Heather A; Tsichlis, Philip N; Struhl, Kevin (2010-09-10). "Loss of miR-200 Inhibition of Suz12 Leads to Polycomb-Mediated Repression Required for the Formation and Maintenance of Cancer Stem Cells". Molecular Cell. 39 (5): 761–772. doi:10.1016/j.molcel.2010.08.013. PMC 2938080. PMID 20832727.
  81. [81]
    Polytarchou, Christos; Iliopoulos, Dimitrios; Struhl, Kevin (2012-08-20). "An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state". PNAS. 109 (36): 14470–14475. doi:10.1073/pnas.1212811109. PMC 3437881. PMID 22908280.
  82. [82]
    Hirsch, Heather A; Iliopoulos, Dimitrios; Tsichlis, Philip N; Struhl, Kevin (2009-10-01). "Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission". Cancer Research. 69 (19): 7507–7511. doi:10.1158/0008-5472.CAN-09-2994. PMC 2756324. PMID 19752085.
  83. [83]
    Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin (2011-04-29). "Metformin Decreases the Dose of Chemotherapy for Prolonging Tumor Remission in Mouse Xenografts Involving Multiple Cancer Cell Types". Cancer Research. 71 (9): 3196–3201. doi:10.1158/0008-5472.CAN-10-3471. PMC 3085572. PMID 21415163.
  84. [84]
    Hirsch, Heather A; Iliopoulos, Dimitrios; Struhl, Kevin (2012-12-31). "Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth". PNAS. 110 (3): 972–977. doi:10.1073/pnas.1221055110. PMC 3549132. PMID 23277563.
  85. [85]
    "American Academy of Arts & Sciences". American Academy of Arts & Sciences. 12 July 2023.
  86. [86]
    "National Academy of Sciences". National Academy of Sciences. 2014.
  87. [87]
    "National Academy of Medicine". National Academy of Medicine. 2015.
  88. [88]
    "Who's Who Lifetime Achievement". Who's Who Lifetime Achievement. 2018-09-13.
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