2013 Fiscal Year Final Research Report
Elucidation for molecular mechanisms of neoplastic cell transformation
| Project/Area Number |
23300347
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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 |
Tumor biology
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| Research Institution | Jikei University School of Medicine (2012-2013)
Tokyo Medical and Dental University (2011) |
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Principal Investigator |
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | DNA傷害 / アポトーシス / ユビキチン化 / プロテオミクス |
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| Research Abstract |
Dysregulation of the G1/S transition in the cell cycle contributes to tumor development. Degradation of c-Jun/c-Myc is a critical process for the G1/S transition. We found DYRK2 functioning as a priming kinase, whose phosphorylation of c-Jun/c-Myc precedes and is required for subsequent GSK3beta phosphorylation. DYRK2 silencing shortened the G1 phase to accelerate cell proliferation due to their escape from ubiquitination-mediated degradation.
EMT plays a fundamental role in the early stages of breast cancer invasion. Snail is an important regulator of EMT. We identified that DYRK2 regulates Snail stability. Knockdown of DYRK2 promoted EMT and cancer invasion in vitro and in vivo.
p53 phosphorylation at Ser46 exerts apoptotic cell death. We found that amphiregulin (AREG) is identified for a direct target of Ser46 phosphorylation. AREG interacted with DDX5. AREG regulated precursor microRNA processing with DDX5 to reduce the expression of anti-apoptotic protein Bcl-2.
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