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- Title
The tumor suppressor p16<sup>INK4a</sup> prevents cell transformation through inhibition of c-Jun phosphorylation and AP-1 activity.
- Authors
Bu Young Choi; Hong Seok Choi; Kwangseok Ko; Yong-Yeon Cho; Feng Zhu; Bong Seok Kang; Ermakova, Svetlana P.; Wei-Ya Ma; Bode, Ann M.; Zigang Dong
- Abstract
Inactivation of the p16INK4a tumor suppressor protein is critical for the development of human cancers, including human melanoma. However, the molecular basis of the protein's inhibitory effect on cancer development is not clear. Here we investigated a possible mechanism for p16INK4a inhibition of neoplastic transformation and UV-induced skin cancer. We show that p16INK4a suppresses the activity of c-Jun N-terminal kinases (JNKs) and that it binds to the glycine-rich loop of the N-terminal domain of JNK3. Although p16INK4a does not affect the phosphorylation of JNKs, its interaction with JNK inhibits c-Jun phosphorylation induced by UV exposure. This, in turn, interferes with cell transformation promoted by the H-Ras–JNK–c-Jun–AP-1 signaling axis.
- Subjects
TUMOR suppressor proteins; CELL transformation; PROTEIN kinases; MELANOMA; SKIN cancer; CARCINOGENESIS; PHOSPHORYLATION; PROMOTERS (Genetics)
- Publication
Nature Structural & Molecular Biology, 2005, Vol 12, Issue 8, p699
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb960