Abstract
The F-box protein Skp2 regulates G1-S transition by controlling p27/Kip.1. The deregulated expression of p27/Kip.1 plays a critical role in the pathogenesis of many human tumors. Its cellular levels depend on ubiquitin-mediated degradation. Recently, Skp2 has been demonstrated to mediate p27/Kip.1 degradation and to have oncogenic properties. In a series of astrocytic gliomas, immunohistochemistry and Western blot of p27/Kip.1 and Skp2 have been compared. p27/Kip.1 decreased with anaplasia and almost disappeared in glioblastomas (GBM), whereas Skp2 was absent or poorly expressed in well differentiated astrocytomas and it was diffusely or focally expressed in most GBM. Since the expression of Skp2 increases during G1-S transition, the correlation of Skp2 levels with malignancy might simply reflect the highest percentage of proliferating cells in anaplastic gliomas or alternatively be instrumental to p27/Kip.1 degradation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Astrocytes / metabolism*
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Astrocytes / pathology
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Astrocytoma / metabolism*
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Astrocytoma / pathology
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Astrocytoma / physiopathology
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Brain / metabolism*
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Brain / pathology
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Brain / physiopathology
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Brain Neoplasms / metabolism*
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Brain Neoplasms / pathology
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Brain Neoplasms / physiopathology
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Cell Cycle Proteins / metabolism*
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Cell Division / physiology
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Cyclin-Dependent Kinase Inhibitor p27
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Cysteine Endopeptidases / metabolism
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Down-Regulation / physiology
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Gene Expression Regulation, Neoplastic / physiology
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Humans
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Immunohistochemistry
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Multienzyme Complexes / metabolism
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Proteasome Endopeptidase Complex
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S-Phase Kinase-Associated Proteins
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Tumor Suppressor Proteins / metabolism*
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Ubiquitin / metabolism
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Up-Regulation / physiology
Substances
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Cell Cycle Proteins
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Multienzyme Complexes
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S-Phase Kinase-Associated Proteins
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Tumor Suppressor Proteins
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Ubiquitin
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Cyclin-Dependent Kinase Inhibitor p27
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex