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Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1).

Perez-Roger, I; Kim, SH; Griffiths, B; Sewing, A; Land, H (1999) Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1). EMBO J, 18 (19). 5310 - 5320. ISSN 0261-4189 https://doi.org/10.1093/emboj/18.19.5310
SGUL Authors: Kim, Soo-Hyun

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Abstract

Cyclin E-Cdk2 kinase activation is an essential step in Myc-induced proliferation. It is presumed that this requires sequestration of G(1) cell cycle inhibitors p27(Kip1) and p21(Cip1) (Ckis) via a Myc-induced protein. We provide biochemical and genetic evidence to show that this sequestration is mediated via induction of cyclin D1 and/or cyclin D2 protein synthesis rates. Consistent with this conclusion, primary cells from cyclin D1(-/-) and cyclin D2(-/-) mouse embryos, unlike wild-type controls, do not respond to Myc with increased proliferation, although they undergo accelerated cell death in the absence of serum. Myc sensitivity of cyclin D1(-/-) cells can be restored by retroviruses expressing either cyclins D1, D2 or a cyclin D1 mutant forming kinase-defective, Cki-binding cyclin-cdk complexes. The sequestration function of D cyclins thus appears essential for Myc-induced cell cycle progression but dispensable for apoptosis.

Item Type: Article
Additional Information: PMCID: PMC1171601
Keywords: 3T3 Cells, Animals, Apoptosis, Base Sequence, CDC2-CDC28 Kinases, Cell Cycle Proteins, Cell Division, Cell Line, Cyclin D1, Cyclin D2, Cyclin E, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, Cyclins, DNA Primers, Enzyme Activation, Mice, Microtubule-Associated Proteins, Protein Binding, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-myc, Rats, Tumor Suppressor Proteins
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: EMBO J
ISSN: 0261-4189
Dates:
DateEvent
1 October 1999Published
PubMed ID: 10508164
Web of Science ID: 10508164
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URI: https://openaccess.sgul.ac.uk/id/eprint/2133
Publisher's version: https://doi.org/10.1093/emboj/18.19.5310

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