Table 1.
Substrates of transcription associated CDKs.
| Transcriptional CDK (partner cyclin/other partner protein) | Substrate(s) | Residue(s) | Downstream effect(s) | Reference(s) |
|---|---|---|---|---|
| CDK7 (cyclin H, MAT1) | RPB1 (C-terminal domain) | Ser5 | Facilitates promoter escape | [7, 8] |
| RPB1 (C-terminal domain) | Ser7 | Recruitment of RPAP2, transcription of snRNA genes | [9] | |
| CDK9 (T-loop domain) | Ser175 | Promotes recruitment of BRD4 | [10] | |
| Thr186 | Enhanced activity | [11] | ||
| CDK12 (T-loop domain) | Thr893 | Enhanced activity | [12] | |
| CDK13 (T-loop domain) | Thr871 | Enhanced activity | [12] | |
| MED1 (C-terminal region) | Thr1457 | Recruitment to chromatin, association with AR and the transcription machinery | [13] | |
| SF3B1 | 18 putative sites (residues 207-434) | Affects association with splicing speckles | [12] | |
| U2AF2 | Unknown | Unknown | [12] | |
| DNA-binding TFs: AR, E2F1, ERα, Ets1, p53, PPARα, PPARγ2, RARα, RARγ, YAP/TAZ, SF1 | Ser515 AR, Ser403/Thr433 E2F1, Ser118 ERα, Thr38 Ets1, Ser33 p53, Ser112 PPARα, Ser12/Ser21 PPARγ2, Ser77 RARα, Ser77/Ser79 RARγ, Ser128/90 YAP/TAZ, Ser203 SF1 | Promotes activity and/or regulation of protein turnover | [14] | |
| CDK8/CDK19 (cyclin C) | Several validated DNA-binding TFs, Mediator subunits, and chromatin regulators (e.g. STAT1, MED12, MED13, SIRT1) | Ser727 STAT1, Ser688 MED12, Ser749 MED13, Thr530 SIRT1 | Context-dependent effects; potentiation of transcriptional activation | [15] |
| CDK9 (cyclin T1) | RPB1 (C-terminal domain) | Ser2 | Promotes transcription elongation | [16] |
| DSIF (Spt5 subunit) | Thr4 | Facilitates promoter-proximal pause release of Pol II | [17] | |
| NELF (NELF-E subunit) | Facilitates promoter-proximal pause release | [18] | ||
| XRN2 | Thr439 | Enhanced cleavage of the RNA transcript from Pol II | [19] | |
| DNA binding TFs: AR, ERα | Ser81, Ser294 | Transcriptional activation in response to ligand | [20, 21] | |
| CDK11 (cyclin L) | AR (N-terminal domain) | Ser308 | Repression of AR transcription | [22] |
| CDK12/CDK13 (cyclin K) | RPB1 (C-terminal domain) | Ser2 | Promotes elongation and the use of distal 3′ transcription termination sites | [23, 40] |
| RPB1 (C-terminal domain) | Ser5 |
CDK cyclin-dependent kinase, RPB1 DNA-directed RNA polymerase II subunit rpb1, MED1 mediator complex subunit 1, SF3B1 splicing factor 3b subunit 1, U2AF2, small nuclear RNA auxiliary factor 2, TF transcription factor, AR androgen receptor, ERα oestrogen receptor alpha; Ets1 ETS proto-oncogene 1, PPAR peroxisome proliferator-activated receptor alpha, RAR retinoic acid receptor, YAP yes-associated protein 1, TAZ transcriptional coactivator with PDZ-binding motif, SF1 splicing factor 1 DSIF DRB sensitivity inducing factor, NELF negative elongation factor, XRN2 5′-3′ exoribonuclease 2, RPAP2 RNA polymerase II-associated protein 2, BRD4 bromodomain-containing protein 4.