PHAPI/pp32 Suppresses Tumorigenesis by Stimulating Apoptosis
| Autor: | Wei Pan, Li S. da Graca, Xuejun Jiang, Hao Wu, Yufang Shao, Qian Yin |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Amino Acid Motifs
Nuclear Localization Signals Apoptosis medicine.disease_cause Biochemistry Mice Molecular Basis of Cell and Developmental Biology medicine Animals Humans Nuclear protein Molecular Biology Caspase Cell Nucleus biology NLRP1 Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins Apoptosis Inducing Factor Nuclear Proteins RNA-Binding Proteins Cell Biology Phosphoproteins Transport protein Cell biology Enzyme Activation Protein Transport Cell nucleus Cell Transformation Neoplastic medicine.anatomical_structure Caspases Mutation biology.protein Apoptosis-inducing factor Carcinogenesis Nuclear localization sequence HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 284:6946-6954 |
| ISSN: | 0021-9258 |
| Popis: | PHAPI/pp32 is a tumor suppressor whose expression is altered in various human cancers. Although PHAPI possesses multiple biochemical activities, the molecular basis for its tumor-suppressive function has remained obscure. Recently we identified PHAPI as an apoptotic enhancer that stimulates apoptosome-mediated caspase activation. In this study, we defined the structural requirement for its activity to stimulate caspase activation using a series of truncation mutants of PHAPI. Further, utilizing these mutants, we provide evidence to support the model that the apoptotic activity of PHAPI is required for its tumor-suppressive capability. Consistently, pp32R1, a close homolog of PHAPI and yet an oncoprotein, is not able to stimulate caspase activation. A highly discrete region between these two proteins localizes to an essential caspase activation motif of PHAPI. Additionally, PHAPI is predominantly a nuclear protein, and it can translocate to the cytoplasm during apoptosis. Disruption of the nuclear localization signal of PHAPI caused a modest decrease of its tumor-suppressive function, indicating that nuclear localization of PHAPI contributes to, but is not essential for, tumor suppression. |
| Databáze: | OpenAIRE |
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