Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase.
Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex
Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655.
Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex.
The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A.
Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155).
Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Interacts with FNIP1 and FNIP2 (PubMed:27353360)
A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to CDK4, 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: 30
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT03065062 | Lung Cancer Squamous Cell, Solid Tumors, Head & Neck Cancer, Pancreatic Cancer | Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors | PHASE1 | SUSPENDED |
| NCT04597580 | Breast Cancer Metastatic, Estrogen Receptor-positive Breast Cancer | Personalised Disease Monitoring in Metastatic Breast Cancer | N/A | ACTIVE_NOT_RECRUITING |
| NCT06243185 | Recurrent Ovarian Carcinoma | Dalpiciclib Combined With Letrozole in HR+/HER2 - Gynecologic Solid Tumors | PHASE2 | UNKNOWN |
| NCT01820364 | Melanoma | LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma | PHASE2 | TERMINATED |
| NCT02494921 | Prostate Cancer | LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC | PHASE1, PHASE2 | COMPLETED |
| NCT07340658 | Advanced, Metastatic Breast Cancer | A Study to Investigate the Efficacy and Safety of Letrozole SIE Compared With Femara® (Both Combined With the CDK4/6 Inhibitor Ribociclib) in Postmenopausal Women With HR-Positive, HER2-Negative, Inoperable Locally Advanced or Metastatic Breast Cancer | PHASE3 | NOT_YET_RECRUITING |
| NCT04494958 | Triple Negative Breast Cancer | Palbociclib and Binimetinib in Advanced Triple Negative Breast Cancer | PHASE1, PHASE2 | COMPLETED |
| NCT03238196 | Metastatic Breast Cancer | Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer | PHASE1 | COMPLETED |
| NCT02297438 | Breast Neoplasms | A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4] | PHASE3 | COMPLETED |
| NCT04584853 | Breast Cancer Female | PreOperative Endocrine Therapy for Individualised Care With Abemaciclib | PHASE3 | ACTIVE_NOT_RECRUITING |