Journal article
Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways
Molecular cancer research, Vol.1(3), pp.195-206
2003
PMID: 12556559
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 G(1)-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.
Details
- Title: Subtitle
- Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways
- Creators
- Lili ZHAO - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United StatesTina SAMUELS - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United StatesSarah WINCKLER - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United StatesChandrashekhar KORGAONKAR - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United StatesVan TOMPKINS - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United StatesMary C HOME - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United StatesDawn E QUELLE - Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- Molecular cancer research, Vol.1(3), pp.195-206
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- PMID
- 12556559
- ISSN
- 1541-7786
- eISSN
- 1557-3125
- Language
- English
- Date published
- 2003
- Academic Unit
- Pathology; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040482302771
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