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Cyclin D3: requirement for G1/S transition and high abundance in quiescent tissues suggest a dual role in proliferation and differentiation

Item Type:Article
Title:Cyclin D3: requirement for G1/S transition and high abundance in quiescent tissues suggest a dual role in proliferation and differentiation
Creators Name:Bartkova, J. and Lukas, J. and Strauss, M. and Bartek, J.
Abstract:The mammalian D-type cyclins D1, D2, and D3 activate the cyclin-dependent kinases CDK4 and CDK6 in G1 and thereby promote the cell's commitment to enter S phase. To elucidate the extent of functional overlap among the D-type cyclins, we have examined several aspects of the least characterized member of this subfamily of G cyclin proteins, cyclin D3. Microinjection of cyclin D3-neutralizing antibody inhibited G1/S transition in human (IMR-90) and rat (R12) diploid fibroblasts, indicating that analogous to cyclins D1 and D2, cyclin D3 is essential for timely progression through G1. In contrast to cyclins D1 and D2, cyclin D3 was (i) ubiquitously expressed among a panel of 70 human cultured cell types; (ii) strongly upregulated upon induction of HL-60 leukaemia cells to differentiate; and (iii) accumulated to high levels in a wide range of quiescent cell types in mouse and human differentiated tissues. Complementary analyses of human biopsies and mouse tissues at different stages of foetal and postnatal development revealed lineage-dependent transient or long-term accumulation of the cyclin D3 protein, correlating with initiation/establishment or maintenance of the mature phenotypes, respectively. Our data support the notion that the biological roles of the individual D-type cyclins are not fully redundant, and suggest a possible dual role for cyclin D3 in cell proliferation and induction and/or maintenance of terminal differentiation.
Keywords:Cell Cycle, Cyclin D3, Cell and Tissue Differentiation, G1/S Transition
Source:Oncogene
ISSN:0950-9232
Publisher:Nature Publishing Group (U.K.)
Volume:17
Number:8
Page Range:1027-1037
Date:27 August 1998
Official Publication:https://doi.org/10.1038/sj.onc.1202016
PubMed:View item in PubMed

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