2013 Fiscal Year Final Research Report
Functional analysis of an atypical nuclear small GTPase in the oncogenic signal
| Project/Area Number |
23570166
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Jichi Medical University (2012-2013)
Nara Institute of Science and Technology (2011) |
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Principal Investigator |
TAGO Kenji 自治医科大学, 医学部, 講師 (20306111)
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| Project Period (FY) |
2011 – 2013
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| Keywords | シグナル伝達 / 発がんシグナル / Gタンパク質 |
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| Research Abstract |
kappaB-Ras is a nuclear-cytoplasmic GTPase that mainly present as GTP-bound form with no stimulating conditions, and its cellular localization is regulated by its bound guanine nucleotides. Here, we found that kappaB-Ras is essential for Ras (G12V)-induced tumorigenesis, although kappaB-Ras itself lacks the oncogenic activities. To clarify the mechanism, by which kappaB-Ras is involved in Ras (G12V)-caused tumorigenesis, we purified the protein complexes including kappaB-Ras2, and identified novel interacting proteins of kappaB-Ras, such as TRB3 and DDB1. TRB3 exhibited the tumor suppressive activity against Ras (G12V). Furthermore, TRB3 induced SUMOylation of kappaB-Ras, and this seems to cause the inhibition of Ras (G12V)-induced transformation. These observations suggest that kappaB-Ras harbors the critical roles in tumorigenesis induced by oncogenic Ras, and this is most likely to be regulated by novel tumor suppressor TRB3 through the SUMOylation of kappaB-Ras.
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