Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism

F. Galbiati, D. Volonte', J. Liu, F. Capozza, P. G. Frank, Liang Zhu, R. G. Pestell, M. P. Lisanti

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

Caveolin-1 is a principal component of caveolae membranes in vivo. Caveolin-1 mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes. Interestingly, the human caveolin-1 gene is localized to a suspected tumor suppressor locus (7q31.1). However, it remains unknown whether caveolin-1 plays any role in regulating cell cycle progression. Here, we directly demonstrate that caveolin-1 expression arrests cells in the G0/G1 phase of the cell cycle. We show that serum starvation induces up-regulation of endogenous caveolin-1 and arrests cells in the G0/G1 phase of the cell cycle. Moreover, targeted down-regulation of caveolin-1 induces cells to exit the G0/G1 phase. Next, we constructed a green fluorescent protein-tagged caveolin-1 (Cav-1-GFP) to examine the effect of caveolin-1 expression on cell cycle regulation. We directly demonstrate that recombinant expression of Cav-1-GFP induces arrest in the G0/G1 phase of the cell cycle. To examine whether caveolin-1 expression is important for modulating cell cycle progression in vivo, we expressed wild-type caveolin-1 as a transgene in mice. Analysis of primary cultures of mouse embryonic fibroblasts from caveolin-1 transgenic mice reveals that caveolin-1 induces 1) cells to exit the S phase of the cell cycle with a concomitant increase in the G0/G1 population, 2) a reduction in cellular proliferation, and 3) a reduction in the DNA replication rate. Finally, we demonstrate that caveolin-1-mediated cell cycle arrest occurs through a p53/p21-dependent pathway. Taken together, our results provide the first evidence that caveolin-1 expression plays a critical role in the modulation of cell cycle progression in vivo.

Original languageEnglish (US)
Pages (from-to)2229-2244
Number of pages16
JournalMolecular Biology of the Cell
Volume12
Issue number8
StatePublished - 2001

Fingerprint

Caveolin 1
Cell Cycle
Cell Cycle Resting Phase
G1 Phase
Caveolins
Caveolae
Starvation
Cell Cycle Checkpoints
Green Fluorescent Proteins
DNA Replication
Transgenes
S Phase
Oncogenes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism. / Galbiati, F.; Volonte', D.; Liu, J.; Capozza, F.; Frank, P. G.; Zhu, Liang; Pestell, R. G.; Lisanti, M. P.

In: Molecular Biology of the Cell, Vol. 12, No. 8, 2001, p. 2229-2244.

Research output: Contribution to journalArticle

Galbiati, F, Volonte', D, Liu, J, Capozza, F, Frank, PG, Zhu, L, Pestell, RG & Lisanti, MP 2001, 'Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism', Molecular Biology of the Cell, vol. 12, no. 8, pp. 2229-2244.
Galbiati, F. ; Volonte', D. ; Liu, J. ; Capozza, F. ; Frank, P. G. ; Zhu, Liang ; Pestell, R. G. ; Lisanti, M. P. / Caveolin-1 expression negatively regulates cell cycle progression by inducing G0/G1 arrest via a p53/p21WAF1/Cip1-dependent mechanism. In: Molecular Biology of the Cell. 2001 ; Vol. 12, No. 8. pp. 2229-2244.
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