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p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Abstract:
Transforming growth factor-beta (TGF-beta) inhibits cell proliferation by inducing a G1-phase cell cycle arrest. Normal progression through G1 is promoted by the activity of the cyclin-dependent protein kinases CDK4 and CDK6 (ref. 2), which are inhibited by the protein p16INK4. We have isolated a new member of the p16INK4 family, p15INK4B. p15 expression is induced approximately 30-fold in human keratinocytes by treatment with TGF-beta, suggesting that p15 may act as an effector of TGF-beta-mediated cell cycle arrest. The gene encoding p15 is located on chromosome 9 adjacent to the p16 gene at a frequent site of chromosomal abnormality in human tumours (9p21).
Insights
Transforming growth factor-beta (TGF-beta) induces cell cycle arrest by upregulating p15INK4B, a new protein in the p16INK4 family. This suggests p15INK4B is a key mediator of TGF-beta
Area of Science:
- Molecular Biology
- Cell Cycle Regulation
- Cancer Genetics
Background:
- Transforming growth factor-beta (TGF-beta) is a key regulator of cell proliferation, inducing G1-phase cell cycle arrest.
- Progression through the G1 phase is controlled by cyclin-dependent protein kinases CDK4 and CDK6, which are inhibited by the p16INK4 protein family.
Purpose of the Study:
- To identify and characterize novel members of the p16INK4 family.
- To investigate the role of new p16INK4 family members in TGF-beta-mediated cell cycle arrest.
Main Methods:
- Isolation and characterization of a new p16INK4 family member, p15INK4B.
- Quantification of p15INK4B gene expression in human keratinocytes treated with TGF-beta.
Main Results:
- A novel p16INK4 family member, designated p15INK4B, was isolated.
- p15INK4B expression was induced approximately 30-fold in human keratinocytes upon TGF-beta treatment.
- The gene encoding p15INK4B is located on chromosome 9p21, a region frequently altered in human tumors, adjacent to the p16 gene.
Conclusions:
- p15INK4B is a novel inhibitor of CDK4/CDK6 and a likely mediator of TGF-beta-induced G1 cell cycle arrest.
- The chromosomal location of p15INK4B (9p21) suggests its potential involvement in tumorigenesis.