Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts

Dawn E Quelle; Richard A Ashmun; Sheila A Shurtleff; Jun-Ya Kato; Dafna Bar-Sagi; Martine F Roussel; Charles J Sherr

doi:10.1101/gad.7.8.1559

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Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts

Journal article

Open access

Peer reviewed

Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts

Dawn E Quelle, Richard A Ashmun, Sheila A Shurtleff, Jun-Ya Kato, Dafna Bar-Sagi, Martine F Roussel and Charles J Sherr

Genes & development, Vol.7(8), pp.1559-1571

08/1993

DOI: 10.1101/gad.7.8.1559

PMID: 8339933

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Abstract

Mammalian D-type cyclins are growth factor-regulated, delayed early response genes that are presumed to control progression through the G1 phase of the cell cycle by governing the activity of cyclin-dependent kinases (cdks). Overexpression of mouse cyclin D1 in serum-stimulated mouse NIH-3T3 and rat-2 fibroblasts increased their rates of G0 to S- and G1- to S-phase transit by several hours, leading to an equivalent contraction of their mean cell generation times. Although such cells remained contact inhibited and anchorage dependent, they manifested a reduced serum requirement for growth and were smaller in size than their normal counterparts. Ectopic expression of cyclin D2 in rodent fibroblasts, either alone or together with exogenous cdk4, shortened their G0- to S-phase interval and reduced their serum dependency, but cyclin D2 alone did not alter cell size significantly. When cells were microinjected during the G1 interval with a monoclonal antibody specifically reactive to cyclin D1, parental rodent fibroblasts and derivatives overexpressing this cyclin were inhibited from entering S phase, but cells injected near the G1/S phase transition were refractory to antibody-induced growth suppression. Thus, cyclin D1, and most likely D2, are rate limiting for G1 progression.

DNA Replication

Gene Expression

Protein Kinases - metabolism

Oncogene Proteins - genetics

Cyclins - genetics

Rats

Cell Size

G1 Phase - drug effects

Cyclin D1

Cyclin-Dependent Kinase 4

Oncogene Proteins - physiology

Cyclin D2

Cyclins - biosynthesis

Animals

Fibroblasts - drug effects

Oncogene Proteins - biosynthesis

Cyclins - physiology

Mice

Proto-Oncogene Proteins

Cyclin-Dependent Kinases

3T3 Cells

Fibroblasts - metabolism

Details

Title: Subtitle: Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts
Creators: Dawn E Quelle - Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Richard A Ashmun
Sheila A Shurtleff
Jun-Ya Kato
Dafna Bar-Sagi
Martine F Roussel
Charles J Sherr
Resource Type: Journal article
Publication Details: Genes & development, Vol.7(8), pp.1559-1571
Publisher: United States
DOI: 10.1101/gad.7.8.1559
PMID: 8339933
ISSN: 0890-9369
eISSN: 1549-5477
Grant note: CA-21765 / NCI NIH HHS CA-55360 / NCI NIH HHS CA-47064 / NCI NIH HHS
Language: English
Date published: 08/1993
Academic Unit: Pathology; Neuroscience and Pharmacology
Record Identifier: 9984040534002771

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