Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:16427012, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094).
Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:16427012, PubMed:20081228, PubMed:20980437, PubMed:21127351, PubMed:9857195). Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169).
Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166, PubMed:28539972). Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166).
Also catalyzes phosphorylation of histone H1.4 (H1-4) at Ser-187' (H1.4S187Ph), a modification associated with transcription activation (PubMed:28539972). The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174).
In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351).
AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:10912001, PubMed:11112772, PubMed:9857195). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670).
Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245)
Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Associates with CCNT1/cyclin-T1, CCNT2/cyclin-T2 (isoform A and isoform B) or CCNK/cyclin-K to form active P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31 and is part of the super elongation complex (SEC).
Component of a complex which is composed of at least 5 members: HTATSF1/Tat-SF1, P-TEFb complex, RNA pol II, SUPT5H and NCL/nucleolin. Associates with UBR5 and forms a transcription regulatory complex composed of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma fibrinogen/FGG) by recruiting their promoters. Component of the 7SK snRNP inactive complex which is composed of at least 8 members: P-TEFb (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, LARP7, BCDIN3, SART3 proteins and 7SK and U6 snRNAs.
This inactive 7SK snRNP complex can also interact with NCOR1 and HDAC3, probably to regulate CDK9 acetylation. Release of P-TEFb from P-TEFb/7SK snRNP complex requires both PP2B to transduce calcium Ca(2+) signaling in response to stimuli (e.g. UV or hexamethylene bisacetamide (HMBA)) and PPP1CA to dephosphorylate Thr-186.
This released P-TEFb remains inactive in the pre-initiation complex with BRD4 until new Thr-186 phosphorylation occurs after the synthesis of a short RNA (PubMed:10393184, PubMed:10574912, PubMed:11884399, PubMed:12037670, PubMed:12065898, PubMed:12718890, PubMed:15965233, PubMed:16109376, PubMed:17452463, PubMed:17643375, PubMed:18249148, PubMed:18483222, PubMed:18566585, PubMed:20159561, PubMed:20471948, PubMed:21127351, PubMed:21779453, PubMed:22195968, PubMed:30134174, PubMed:9491887). Interacts with BRD4; to target chromatin binding (PubMed:16109376, PubMed:16109377, PubMed:18483222). Interacts with JMJD6 (PubMed:24360279).
Interacts with activated nuclear STAT3 and RELA/p65 (PubMed:17956865, PubMed:18362169). Binds to AR and MYOD1 (PubMed:12037670, PubMed:20980437). Forms a complex composed of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes (PubMed:20081228).
The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (By similarity). Interacts with HSF1 (PubMed:27189267). Interacts with TBX21 (By similarity).
Isoform 3: binds to KU70/XRCC6 (PubMed:20535204). Interacts with WDR43 (By similarity). Interacts with ZMYND8; the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (PubMed:30134174)
(Microbial infection) Interacts with the acidic/proline-rich region of HIV-1 and HIV-2 Tat via T-loop region and is thus required for HIV to hijack host transcription machinery during its replication through cooperative binding to viral TAR RNA
(Microbial infection) Interacts with human herpes virus 1 (HHV-1) protein ICP22; this interaction blocks the recruitment of positive transcription elongation factor b (P-TEFb) to the viral promoter
Ubiquitous
No mutation information available.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CDK9, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 7
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT03263637 | Relapsed or Refractory Haematological Malignancies Including, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Lymphocytic Leukemia, High Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Richter's Syndrome, B-cell Non-Hodgkin Lymphoma, T-cell Non-Hodgkin Lymphoma, Small Lymphocytic Lymphoma, Multiple Myeloma | Study to Assess Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AZD4573 in Relapsed/Refractory Haematological Malignancies | PHASE1 | COMPLETED |
| NCT05665530 | Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Mantle Cell Lymphoma (MCL), Richter's Syndrome, T-cell Lymphoma, Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma, Myeloid Malignancies, Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML), Myelodysplastic Syndrome (MDS), MDS/Myeloproliferative Neoplasm (MPN) Overlap Syndrome | A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With R/R Hematologic Malignancies | PHASE1 | COMPLETED |
| NCT02745743 | Hematologic Neoplasms | Phase I Trial of BAY1251152 for Advanced Blood Cancers | PHASE1 | COMPLETED |
| NCT04978779 | Relapsed Non Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia, Richter Syndrome, MYC Amplification, MYC Overexpression, MYC Translocation | A Study to Evaluate VIP152 in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome | PHASE1 | TERMINATED |
| NCT04718675 | Relapsed Solid Tumors, Refractory Solid Tumors, Non-Hodgkin Lymphoma, HGSOC, Platinum Resistant High Grade Serous Ovarian Cancer | A Study of KB-0742 in Participants With Relapsed or Refractory Solid Tumors Including Platinum Resistant High Grade Serous Ovarian Cancer (HGSOC) | PHASE1, PHASE2 | TERMINATED |
| NCT05159518 | Sarcoma, Castrate Resistant Prostate Cancer, Hormone Receptor Positive HER2 Negative Breast Cancer, Non-small Cell Lung Cancer, Solid Tumors With Known MYC Amplification | A Study of PRT2527 in Participants With Advanced Solid Tumors | PHASE1 | COMPLETED |
| NCT04588922 | Hematologic Malignancies | Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML | PHASE1, PHASE2 | RECRUITING |