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. 1999 Oct 1;18(19):5310-20.
doi: 10.1093/emboj/18.19.5310.

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

I Perez-Roger  1 , S H Kim, B Griffiths, A Sewing, H Land
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Cyclins D1 and D2 mediate myc-induced proliferation via sequestration of p27(Kip1) and p21(Cip1)

I Perez-Roger et al. EMBO J. .

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.

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