Deregulations in the Cyclin-Dependent Kinase-9-Related Pathway in Cancer: Implications for Drug Discovery and Development

Table 2

Properties of cyclin-dependent kinases and binding partners in mammalian cell biology.

Cyclin-dependent kinases (Cdks)	Most important binding partners for Cdks (secondary binding partners are indicated between parenthesis)	List of major factors that interact with the heterodimer Cdk/cyclin partner	Functions of the heterodimer Cdk/cyclin partner in mammalian cell biology	Bibliographic references
Cdk1	Cyclins A1; A2; B1; B2; (E; B3)	Cell cycle machinery; Cdc28-dependent kinase subunit (Cks)	G2-M (cell cycle)	[13]
Cdk2	Cyclins A1; A2; E1; E2 (D1; D2; B1; B3)	Cell cycle machinery; protein kinase C-(PKC)-ι	G1-S (cell cycle)	[13, 14]
Cdk3	Cyclins E1; E2; A1; A2; C	Cell cycle machinery; E2F/dimerization partner (DP)	G0-G1-S (cell cycle)	[13]
Cdk4	Cyclins D1; D2; D3	Cell cycle machinery; MyoD	G1-S (cell cycle)	[13]
Cdk5	p35; p39 (cyclins D; E; G)	—	Senescence; inhibition of cell cycle reentry in postmitotic neurons; neuronal migration; formation of dendrite extensions and synapses; neuronal survival; neuronal death	[13–22]
Cdk6	Cyclins D1; D2; D3	Cell cycle machinery	G1-S (cell cycle)	[13]
Cdk7	Cyclin H and MAT	RNA pol II; Protein kinase C- (PKC-) ι; estrogen receptor-α	Transcription; Cdk-activating kinase (CAK)	[13, 14, 26–29]
Cdk8	Cyclin C (K?)	RNA pol II; Smad	Transcription	[23]
Cdk9	Cyclins T1; T2a; T2b; K	RNA pol II; MyoD; p53; retinoblastomas gene (pRb); hSPT5, c-Myc; SkiP; Smad; signal transducer and activator of transcription 3 (STAT3); TRAF2; Brd4; NF-𝜅B; Suppressor of Ty Homolog-5 (SUPT5H); Negative Elongation Factor-E (NELF-E); human Rad6 homolog UBE2A; E12/E47 (members of the basic helix-loop-helix family); Hexamethylene bisacetamide-inducible protein 1 (Hexim1); Hexim2; 7SK snRNA; p300/GATA4, HIV-1 and HIV-2 Tat protein; HTLV-1 tax protein; EBV EBNA2; hCMV pUL69; hCMV IE2; HSV-1 ICP22 and ICP27; adenovirus large E1A (L-E1A) protein; influenza virus RNA-dependent RNA polymerase (vRNP); gp130*; HSP70*; HSP90*; Cdc37* (*these factors form a transient association with the monomeric Cdk9)	Transcription; cotranscriptional mRNA processing; regulation of chromatin modification; cell differentiation (B and T lymphocytes, muscle cells); adipogenesis; protection from apoptosis	[3, 10, 12, 13, 24–28, 56–67, 78, 79, 85, 88–107]
Cdk10	Unidentified	Ets2	Transcription; G2M (cell cycle)	[30–35]
Cdk11	Cyclins L1; L2; (D)	Cell cycle machinery; RNA pol II; RanBPM; RNPS1; CK2; 14-3-3; 9G8; elF3; NOT2; HBO1	Transcription; pre-mRNA splicing; M (cell cycle)	[13, 36–41]
Cdk12	Cyclins L1; L2; K	RNA pol II;	Transcription; regulation of RNA splicing; genome stability	[42–46]
Cdk13	Cyclins L1; L2; K	RNA pol II;	Transcription; regulation of RNA splicing	[42–46]
Cdk14	Cyclins D1; D2; D3; Y	—	Cell cycle progression; cell proliferation; cell motility; chemoresistance in human primary oesophageal squamous cell carcinoma cells	[47–55]