G1/S-specific cyclin-D1

Function

Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex 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 a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner.

Classification

Family (Pfam)

PF02984 Cyclin_C, PF00134 Cyclin_N

InterPro

Cyclin, Cyclin-like_dom, Cyclin-like_sf, Cyclin_C-dom, Cyclin_N, Cyclins_cyclin-box

Functional cluster

Zinc-Finger Nucleic-Acid-Binding & Methyltransferases

Experimental structures · PDB · 11

• 2W96 X-ray 2.30A
• 2W99 X-ray 2.80A
• 2W9F X-ray 2.85A
• 2W9Z X-ray 2.45A
• 5VZU X-ray 2.70A
• 6P8E X-ray 2.30A
• 6P8F X-ray 2.89A
• 6P8G X-ray 2.80A
• 6P8H X-ray 3.19A
• 9CSK X-ray 2.25A
• 9IVD EM 3.55A

A predicted model is available from AlphaFold.

Gene Ontology · 44

• GO:0005923 bicellular tight junction
• GO:0000307 cyclin-dependent protein kinase holoenzyme complex
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005815 microtubule organizing center
• GO:0031965 nuclear membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0017053 transcription repressor complex
• GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity
• GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity
• GO:0019899 enzyme binding
• GO:0042826 histone deacetylase binding
• GO:0070064 proline-rich region binding
• GO:0004672 protein kinase activity
• GO:0019901 protein kinase binding
• GO:0043539 protein serine/threonine kinase activator activity
• GO:0044877 protein-containing complex binding
• GO:0003714 transcription corepressor activity
• GO:0031100 animal organ regeneration
• GO:0051301 cell division
• GO:0071456 cellular response to hypoxia
• GO:0006974 DNA damage response
• GO:0006351 DNA-templated transcription
• GO:0000082 G1/S transition of mitotic cell cycle
• GO:0033327 Leydig cell differentiation
• GO:0001889 liver development
• GO:0031571 mitotic G1 DNA damage checkpoint signaling
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0008284 positive regulation of cell population proliferation
• GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
• GO:0010971 positive regulation of G2/M transition of mitotic cell cycle
• GO:0051592 response to calcium ion
• GO:0051412 response to corticosterone
• GO:0032355 response to estradiol
• GO:0043627 response to estrogen
• GO:0045471 response to ethanol
• GO:0010039 response to iron ion
• GO:0044321 response to leptin
• GO:0032026 response to magnesium ion
• GO:0070141 response to UV-A
• GO:0033197 response to vitamin E
• GO:0010165 response to X-ray
• GO:0009410 response to xenobiotic stimulus

Disease associations

• plasma cell myeloma MONDO:0009693

Drugs targeting this protein · 2

• BRICICLIB inhibitor
• PALBOCICLIB inhibitor

Related proteins · sequence + function similarity

• G1/S-specific cyclin-D1 1.00
• G1/S-specific cyclin-D1 0.99
• G1/S-specific cyclin-D1 0.99
• G1/S-specific cyclin-D1 0.99
• G1/S-specific cyclin-D1 0.99
• G1/S-specific cyclin-D1 0.96
• G1/S-specific cyclin-D2 0.96
• G1/S-specific cyclin-D1 0.96
• G1/S-specific cyclin-D2 0.96
• G1/S-specific cyclin-D2 0.96
• G1/S-specific cyclin-D1 0.96
• G1/S-specific cyclin-D2 0.95

Co-cited proteins · studied together in the literature

• Cyclin-dependent kinase 4 5 shared papers
• F-box only protein 32 1 shared papers
• F-box only protein 31 2 shared papers
• Insulinoma-associated protein 1 3 shared papers
• Ubiquitin carboxyl-terminal hydrolase 2 1 shared papers
• Transmembrane 4 L6 family member 5 1 shared papers
• F-box/WD repeat-containing protein 8 1 shared papers
• G1/S-specific cyclin-E1 2 shared papers
• G1/S-specific cyclin-D3 4 shared papers
• G1/S-specific cyclin-D2 3 shared papers
• G1/S-specific cyclin-D2 2 shared papers
• G1/S-specific cyclin-D3 2 shared papers

Literature · 28 cited papers

• F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive cancer progression. Nat. Commun. · 2025
• The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D. Nature · 2021
• CRL4AMBRA1 is a master regulator of D-type cyclins. Nature · 2021
• AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature · 2021
• Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCFFBXO31 ubiquitin ligase. Proc. Natl. Acad. Sci. U.S.A. · 2018
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor. Cell Cycle · 2011
• TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression and RhoA activity. Biochim. Biophys. Acta · 2010
• Suppression of cancer cell growth by promoting cyclin D1 degradation. Mol. Cell · 2009
• F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature · 2009
• Crystal structure of human CDK4 in complex with a D-type cyclin. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest. J. Biol. Chem. · 2009
• … and 16 more in the literature graph