Regulation of G1 Cell Cycle Progression: Distinguishing the Restriction Point from a Nutrient-Sensing Cell Growth Checkpoint(s)
- 1 November 2010
- journal article
- Published by SAGE Publications in Genes & Cancer
- Vol. 1 (11), 1124-1131
- https://doi.org/10.1177/1947601910392989
Abstract
Most genetic changes that promote tumorigenesis involve dysregulation of G1 cell cycle progression. A key regulatory site in G1 is a growth factor-dependent restriction point (R) where cells commit to mitosis. In addition to the growth factor-dependent "R," which maps to a site about 3.5 hours after mitosis, there is another checkpoint later in G1 that is dependent on nutritional sufficiency that has also been referred to as R. However, this second site in late G1 can be distinguished both temporally and genetically from R. We are proposing that the late G1 regulatory site be more appropriately referred to as a "cell growth" checkpoint to distinguish it from R. This checkpoint, which likely has an evolutionary relationship to the yeast cell cycle checkpoint START, is regulated by signals governed by mTOR, the mammalian target of rapamycin. This review summarizes evidence that distinguishes R from the proposed cell growth checkpoint. Since both checkpoints are dysregulated in most, if not all, human cancers, distinguishing between these 2 distinct G1 regulatory checkpoints has significance for rational therapeutic strategies targeting oncogenic signals.Keywords
This publication has 81 references indexed in Scilit:
- Amino acid regulation of TOR complex 1American Journal of Physiology-Endocrinology and Metabolism, 2009
- Regulation of mTORC1 and mTORC2 Complex Assembly by Phosphatidic Acid: Competition with RapamycinMolecular and Cellular Biology, 2009
- [Can defective TGF-Beta signaling be an Achilles heel in human cancer?].2008
- The TSC1–TSC2 complex: a molecular switchboard controlling cell growthBiochemical Journal, 2008
- Multiple pathways regulated by the tumor suppressor PP2A in transformationTrends in Molecular Medicine, 2008
- Defective TGF-β signaling sensitizes human cancer cells to rapamycinOncogene, 2007
- Novel roles of Akt and mTOR in suppressing TGF-β/ALK5-mediated Smad3 activationThe EMBO Journal, 2005
- Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell TransformationMolecular and Cellular Biology, 2002
- Defective repression of c- myc in breast cancer cells: A loss at the core of the transforming growth factor β growth arrest programProceedings of the National Academy of Sciences of the United States of America, 2001
- Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene familyCell, 1991