The tumor suppressor p16INK4a prevents cell transformation through inhibition of c-Jun phosphorylation and AP-1 activity
| Autor: | Kwangseok Ko, Zigang Dong, Bu Young Choi, Feng Zhu, Bong Seok Kang, Yong-Yeon Cho, Wei-Ya Ma, Hong Seok Choi, Ann M. Bode, Svetlana P. Ermakova |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Skin Neoplasms Genetic Vectors Immunoblotting Cell Fluorescent Antibody Technique Plasma protein binding Biology law.invention Mice Mitogen-Activated Protein Kinase 10 Structural Biology law Cell Line Tumor Two-Hybrid System Techniques medicine Animals Humans Neoplastic transformation Phosphorylation Melanoma Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Glutathione Transferase Kinase Cell biology Transcription Factor AP-1 Transformation (genetics) Cell Transformation Neoplastic medicine.anatomical_structure Cell culture Suppressor Protein Binding Signal Transduction |
| Zdroj: | Nature Structural & Molecular Biology. 12:699-707 |
| ISSN: | 1545-9985 1545-9993 |
| Popis: | Inactivation of the p16(INK4a) 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 p16(INK4a) inhibition of neoplastic transformation and UV-induced skin cancer. We show that p16(INK4a) 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 p16(INK4a) 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. |
| Databáze: | OpenAIRE |
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