CCND1

CCND1 encodes cyclin D1, a 295-residue, non-catalytic D-type cyclin that couples mitogenic signalling to cell-cycle commitment. Its cyclin box binds CDK4 or CDK6 to form a serine/threonine kinase holoenzyme in which cyclin D1 supplies the activating conformational change and the substrate specificity; the assembled complex phosphorylates the retinoblastoma family pocket proteins RB1, RBL1 and RBL2 in G1, releasing E2F transcription factors and licensing the G1/S transition, after which cyclin E-CDK2 completes RB inactivation. Cyclin D1 itself has no kinase activity. Its abundance, rather than its intrinsic activity, is the regulated variable: RAS-RAF-MEK-ERK signalling induces CCND1 transcription while PI3K-AKT supports translation and complex assembly, and CIP/KIP proteins (p21, p27) promote holoenzyme assembly and carry it through the nuclear membrane into the nucleus. At the G1/S boundary, GSK3-dependent phosphorylation of Thr286 drives XPO1-mediated nuclear export followed by ubiquitination - chiefly by CRL4(AMBRA1), and by SCF(FBXO4), SCF(FBXO31) after DNA damage, APC/C-CDC27 and UHRF2 - and proteasomal degradation, while USP2 deubiquitination and FBXO32-mediated K27-linked ubiquitination stabilise it. Beyond the kinase, cyclin D1 has CDK-independent activities as a transcriptional corepressor: tethered by INSM1 it delivers HDAC1/HDAC3 to the NEUROD1 and insulin promoters, and it restrains the androgen receptor and NRF1. Cyclin D1 is nuclear, cytoplasmic and nuclear-membrane associated, is required in a tissue-restricted way for retinal and pregnancy-associated mammary development, and is a prominent oncogene: it is amplified or overexpressed in many carcinomas and is placed under immunoglobulin-locus control by t(11;14)(q13;q32) in mantle-cell lymphoma and multiple myeloma.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.