2009 Fiscal Year Final Research Report
Analysis of cellular signal transduction via Neurofibromatosis tumor suppressor gene products and development of their clinical targets
| Project/Area Number |
19390382
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
ARAKI Norie Kumamoto University, 大学院・生命科学研究部, 准教授 (80253722)
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| Co-Investigator(Renkei-kenkyūsha) |
SAYA Hideyuki 慶應義塾大学, 医学部, 教授 (80264282)
NAKAMURA Hideo 熊本大学, 医学部附属病院, 助教 (30359963)
KOBAYASHI Daiki 熊本大学, 大学院・生命科学研究部, 研究員 (20448517)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 脳腫瘍学 / プロテオミクス / NF1 / NF2 / 神経系腫瘍 / 細胞分化 |
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| Research Abstract |
Neurofibromatosis (NF) tumor suppressor gene products, neurofibromin : NF1 and merlin : NF2, are though to be important regulators of cellular growth, differentiation, and apoptosis, and implicated in the neural abnormality of NF patients. However, the precise cellular function of NF proteins has yet to be clarified. In this study, we utilized proteomic strategies, functional annotation with a proprietary gene ontology (MANGO), and standard biochemical methods to identify proteins related to neuronal differentiation in PC12 cells, which serve as a representative model system for studying NF related neuronal biological processes. Of 1,600 non-redundant proteins quantitatively identified, 72 were novel nerve growth factor-responsive PC12 proteins mostly related to the biological processes of cell morphogenesis, apoptosis/survival, and cell differentiation. Using these proteomic strategies and database, we identified a set of NF-associating cellular proteins, including axon regulator CRMP-2. These associations were crucial for the axon formation in neuron and were regulated by a series of kinase activations by CDK5, GSK-3b, and Rho kinase being controlled by neurofibromin. Our study demonstrates that the functional association of NF proteins and their associating proteins are essential for neuronal cell differentiation and that lack of expression or abnormal regulation of NF proteins can result in impaired function of neural cells, which is likely a factor in NF-related pathogenesis.
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[Journal Article] Neurofibromatosis Type I tumor suppressor, neurofibromin, regulates the neurite outgrowth of PC12 cells via its associating protein, CRMP-22008
Author(s)
Patrakitkomjorn S, Kobayashi D, Morikawa T, Wilson MM, Tsubota N, Irie A, Ozawa T, Aoki M, Arimura N, Kaibuchi K, Saya H, Araki N
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Journal Title
J. Biol. Chem 283(14)
Pages: 9399-413
Peer Reviewed
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