Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways

Lili Zhao, Tina Samuels, Sarah Winckler, Chandrashekhar Korgaonkar, Van Tompkins, Mary C Horne, Dawn E. Quelle

Research output: Contribution to journalArticle

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Abstract

Cyclin G1 is a p53-responsive gene that is induced in alternative reading frame (ARF)-arrested cells, yet its role in growth control is unclear. We tested its effects on growth and involvement in the ARF-Mdm2-p53 tumor suppressor pathway. We show that cyclin G1 interacts with ARF, Mdm2, and p53 in vitro and in vivo. At high levels, cyclin G1 induces a G1-phase arrest in mammalian cells that coincides with p53 activation. Conversely, lower levels of cyclin G1 lack intrinsic growth inhibitory effects yet potentiate ARF-mediated growth arrest. Notably, cyclin G1 is down-regulated by Mdm2 through proteasome-mediated degradation. These data suggest that cyclin G1 is a positive feedback regulator of p53 whose expression is restrained by Mdm2. Interestingly, growth inhibition by cyclin G1 does not require p53 but instead exhibits partial retinoblastoma protein (pRb) dependence. These findings reveal that cyclin G1 has growth inhibitory activity that is mechanistically linked to ARF-p53 and pRb tumor suppressor pathways.

Original languageEnglish (US)
Pages (from-to)195-206
Number of pages12
JournalMolecular Cancer Research
Volume1
Issue number3
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Cyclin G1
Reading Frames
Retinoblastoma Protein
Growth
Neoplasms
p53 Genes
G1 Phase
Proteasome Endopeptidase Complex

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Zhao, L., Samuels, T., Winckler, S., Korgaonkar, C., Tompkins, V., Horne, M. C., & Quelle, D. E. (2003). Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways. Molecular Cancer Research, 1(3), 195-206.

Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways. / Zhao, Lili; Samuels, Tina; Winckler, Sarah; Korgaonkar, Chandrashekhar; Tompkins, Van; Horne, Mary C; Quelle, Dawn E.

In: Molecular Cancer Research, Vol. 1, No. 3, 01.01.2003, p. 195-206.

Research output: Contribution to journalArticle

Zhao, L, Samuels, T, Winckler, S, Korgaonkar, C, Tompkins, V, Horne, MC & Quelle, DE 2003, 'Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways', Molecular Cancer Research, vol. 1, no. 3, pp. 195-206.
Zhao L, Samuels T, Winckler S, Korgaonkar C, Tompkins V, Horne MC et al. Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways. Molecular Cancer Research. 2003 Jan 1;1(3):195-206.
Zhao, Lili ; Samuels, Tina ; Winckler, Sarah ; Korgaonkar, Chandrashekhar ; Tompkins, Van ; Horne, Mary C ; Quelle, Dawn E. / Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways. In: Molecular Cancer Research. 2003 ; Vol. 1, No. 3. pp. 195-206.
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