Anshabo et al.

CDK9 in Cancer

26. Garber ME, Wei P, KewalRamani VN, Mayall TP, Herrmann CH, Rice AP, 45. McCracken S, Fong N, Yankulov K, Ballantyne S, Pan G, Greenblatt J, et al.
et al. The Interaction Between HIV-1 Tat and Human Cyclin T1 Requires The C-terminal Domain of RNA Polymerase II Couples mRNA Processing
Zinc and a Critical Cysteine Residue That is Not Conserved in the Murine to Transcription. Nature (1997) 385(6614):357–61. doi: 10.1038/385357a0
CycT1 Protein. Genes Dev (1998) 12(22):3512–27. doi: 10.1101/ 46. Harlen KM, Churchman LS. The Code and Beyond: Transcription
gad.12.22.3512 Regulation by the RNA Polymerase II Carboxy-Terminal Domain. Nat
27. Jang MK, Mochizuki K, Zhou M, Jeong HS, Brady JN, Ozato K. The Rev Mol Cell Biol (2017) 18(4):263–73. doi: 10.1038/nrm.2017.10
Bromodomain Protein Brd4 is a Positive Regulatory Component of P- 47. Gu B, Eick D, Bensaude O. CTD Serine-2 Plays a Critical Role in Splicing
TEFb and Stimulates RNA Polymerase II-dependent Transcription. Mol Cell and Termination Factor Recruitment to RNA Polymerase II In Vivo. Nucleic
(2005) 19(4):523–34. doi: 10.1016/j.molcel.2005.06.027 Acids Res (2013) 41(3):1591–603. doi: 10.1093/nar/gks1327
28. Taube R, Lin X, Irwin D, Fujinaga K, Peterlin BM. Interaction Between P- 48. Krogan NJ, Kim M, Tong A, Golshani A, Cagney G, Canadien V, et al.
TEFb and the C-terminal Domain of RNA Polymerase II Activates Methylation of Histone H3 by Set2 in Saccharomyces Cerevisiae is Linked to
Transcriptional Elongation From Sites Upstream or Downstream of Transcriptional Elongation by RNA Polymerase II. Mol Cell Biol (2003) 23
Target Genes. Mol Cell Biol (2002) 22(1):321–31. doi: 10.1128/ (12):4207–18. doi: 10.1128/mcb.23.12.4207-4218.2003
mcb.22.1.321-331.2002 49. Li B, Howe L, Anderson S, Yates JR,3, Workman JL. The Set2 Histone
29. Kiernan RE, Emiliani S, Nakayama K, Castro A, Labbe JC, Lorca T, et al. Methyltransferase Functions Through the Phosphorylated Carboxyl-
Interaction Between Cyclin T1 and SCF(SKP2) Targets CDK9 for Terminal Domain of RNA Polymerase II. J Biol Chem (2003) 278
Ubiquitination and Degradation by the Proteasome. Mol Cell Biol (2001) (11):8897–903. doi: 10.1074/jbc.M212134200
21(23):7956–70. doi: 10.1128/MCB.21.23.7956-7970.2001 50. Qiu H, Hu C, Gaur NA, Hinnebusch AG. Pol II CTD Kinases Bur1 and
30. Fu TJ, Peng J, Lee G, Price DH, Flores O. Cyclin K Functions as a CDK9 Kin28 Promote Spt5 CTR-Independent Recruitment of Paf1 Complex.
Regulatory Subunit and Participates in RNA Polymerase II Transcription. EMBO J (2012) 31(16):3494–505. doi: 10.1038/emboj.2012.188
J Biol Chem (1999) 274(49):34527–30. doi: 10.1074/jbc.274.49.34527 51. Devaiah BN, Lewis BA, Cherman N, Hewitt MC, Albrecht BK, Robey PG,
31. Baumli S, Hole AJ, Noble ME, Endicott JA. The CDK9 C-Helix Exhibits et al. BRD4 is an Atypical Kinase That Phosphorylates Serine2 of the RNA
Conformational Plasticity That may Explain the Selectivity of CAN508. ACS Polymerase II Carboxy-Terminal Domain. Proc Natl Acad Sci USA (2012)
Chem Biol (2012) 7(5):811–6. doi: 10.1021/cb2004516 109(18):6927–32. doi: 10.1073/pnas.1120422109
32. Sims RJ,3, Belotserkovskaya R, Reinberg D. Elongation by RNA Polymerase 52. Bartkowiak B, Liu P, Phatnani HP, Fuda NJ, Cooper JJ, Price DH, et al.
II: The Short and Long of it. Genes Dev (2004) 18(20):2437–68. doi: 10.1101/ CDK12 is a Transcription Elongation-Associated CTD Kinase, the
gad.1235904 Metazoan Ortholog of Yeast Ctk1. Genes Dev (2010) 24(20):2303–16.
33. Saunders A, Core LJ, Lis JT. Breaking Barriers to Transcription Elongation. doi: 10.1101/gad.1968210
Nat Rev Mol Cell Biol (2006) 7(8):557–67. doi: 10.1038/nrm1981 53. Liang K, Gao X, Gilmore JM, Florens L, Washburn MP, Smith E, et al.
34. Zhou Q, Li T, Price DH. RNA Polymerase II Elongation Control. Annu Rev Characterization of Human Cyclin-Dependent Kinase 12 (CDK12) and
Biochem (2012) 81:119–43. doi: 10.1146/annurev-biochem-052610-095910 CDK13 Complexes in C-terminal Domain Phosphorylation, Gene
35. Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, et al. c-Myc Transcription, and RNA Processing. Mol Cell Biol (2015) 35(6):928–38.
Regulates Transcriptional Pause Release. Cell (2010) 141(3):432–45. doi: 10.1128/MCB.01426-14
doi: 10.1016/j.cell.2010.03.030 54. Shao W, Zeitlinger J. Paused RNA Polymerase II Inhibits New Transcriptional
36. Adelman K, Lis JT. Promoter-Proximal Pausing of RNA Polymerase II: Initiation. Nat Genet (2017) 49(7):1045–51. doi: 10.1038/ng.3867
Emerging Roles in Metazoans. Nat Rev Genet (2012) 13(10):720–31. 55. Gressel S, Schwalb B, Decker TM, Qin W, Leonhardt H, Eick D, et al. CDK9-
doi: 10.1038/nrg3293 Dependent RNA Polymerase II Pausing Controls Transcription Initiation.
37. Wada T, Takagi T, Yamaguchi Y, Watanabe D, Handa H. Evidence That P- Elife (2017) 6:1–24. doi: 10.7554/eLife.29736
TEFb Alleviates the Negative Effect of DSIF on RNA Polymerase II- 56. Laitem C, Zaborowska J, Isa NF, Kufs J, Dienstbier M, Murphy S. CDK9
dependent Transcription In Vitro. EMBO J (1998) 17(24):7395–403. Inhibitors Define Elongation Checkpoints At Both Ends of RNA Polymerase
doi: 10.1093/emboj/17.24.7395 II-transcribed Genes. Nat Struct Mol Biol (2015) 22(5):396–403.
38. Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, et al. doi: 10.1038/nsmb.3000
NELF, a Multisubunit Complex Containing RD, Cooperates With DSIF to 57. Sanso M, Levin RS, Lipp JJ, Wang VY, Greifenberg AK, Quezada EM, et al.
Repress RNA Polymerase II Elongation. Cell (1999) 97(1):41–51. P-TEFb Regulation of Transcription Termination Factor Xrn2 Revealed by a
doi: 10.1016/s0092-8674(00)80713-8 Chemical Genetic Screen for Cdk9 Substrates. Genes Dev (2016) 30(1):117–
39. Fujinaga K, Irwin D, Huang Y, Taube R, Kurosu T, Peterlin BM. Dynamics 31. doi: 10.1101/gad.269589.115
of Human Immunodeficiency Virus Transcription: P-TEFb Phosphorylates 58. Parua PK, Booth GT, Sanso M, Benjamin B, Tanny JC, Lis JT, et al. A Cdk9-
RD and Dissociates Negative Effectors From the Transactivation Response PP1 Switch Regulates the Elongation-Termination Transition of RNA
Element. Mol Cell Biol (2004) 24(2):787–95. doi: 10.1128/mcb.24.2.787- Polymerase II. Nature (2018) 558(7710):460–4. doi: 10.1038/s41586-018-
795.2004 0214-z
40. Kim JB, Sharp PA. Positive Transcription Elongation Factor B 59. Garriga J, Bhattacharya S, Calbo J, Marshall RM, Truongcao M, Haines DS,
Phosphorylates hSPT5 and RNA Polymerase II Carboxyl-Terminal et al. CDK9 is Constitutively Expressed Throughout the Cell Cycle, and its
Domain Independently of Cyclin-Dependent Kinase-Activating Kinase. Steady-State Expression is Independent of SKP2. Mol Cell Biol (2003) 23
J Biol Chem (2001) 276(15):12317–23. doi: 10.1074/jbc.M010908200 (15):5165–73. doi: 10.1128/mcb.23.15.5165-5173.2003
41. Yamada T, Yamaguchi Y, Inukai N, Okamoto S, Mura T, Handa H. P-TEFb- 60. Bettencourt-Dias M, Giet R, Sinka R, Mazumdar A, Lock WG, Balloux F,
mediated Phosphorylation of Hspt5 C-terminal Repeats is Critical for et al. Genome-Wide Survey of Protein Kinases Required for Cell Cycle
Processive Transcription Elongation. Mol Cell (2006) 21(2):227–37. Progression. Nature (2004) 432(7020):980–7. doi: 10.1038/nature03160
doi: 10.1016/j.molcel.2005.11.024 61. Zhao R, Nakamura T, Fu Y, Lazar Z, Spector DL. Gene Bookmarking
42. Shim EY, Walker AK, Shi Y, Blackwell TK. CDK-9/Cyclin T (P-TEFb) is Accelerates the Kinetics of Post-Mitotic Transcriptional Re-Activation. Nat
Required in Two Postinitiation Pathways for Transcription in the C. Elegans Cell Biol (2011) 13(11):1295–304. doi: 10.1038/ncb2341
Embryo. Genes Dev (2002) 16(16):2135–46. doi: 10.1101/gad.999002 62. Yang Z, He N, Zhou Q. Brd4 Recruits P-TEFb to Chromosomes At Late
43. Ni Z, Schwartz BE, Werner J, Suarez JR, Lis JT. Coordination of Mitosis to Promote G1 Gene Expression and Cell Cycle Progression. Mol
Transcription, RNA Processing, and Surveillance by P-TEFb Kinase on Cell Biol (2008) 28(3):967–76. doi: 10.1128/MCB.01020-07
Heat Shock Genes. Mol Cell (2004) 13(1):55–65. doi: 10.1016/s1097-2765 63. Dey A, Nishiyama A, Karpova T, McNally J, Ozato K. Brd4 Marks Select
(03)00526-4 Genes on Mitotic Chromatin and Directs Postmitotic Transcription. Mol
44. Czudnochowski N, Bosken CA, Geyer M. Serine-7 But Not Serine-5 Biol Cell (2009) 20(23):4899–909. doi: 10.1091/mbc.E09-05-0380
Phosphorylation Primes RNA Polymerase II CTD for P-TEFb 64. Mochizuki K, Nishiyama A, Jang MK, Dey A, Ghosh A, Tamura T, et al. The
Recognition. Nat Commun (2012) 3:842. doi: 10.1038/ncomms1846 Bromodomain Protein Brd4 Stimulates G1 Gene Transcription and

Frontiers in Oncology | www.frontiersin.org 19 May 2021 | Volume 11 | Article 678559