The open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells

• Project/Area Number: 26860780
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: WATANABE YUKO 東北大学, 大学病院, 助教 (40610671)
• Research Collaborator: SASAHARA YOJI 東北大学, 大学院医学系研究科, 准教授 (60372314)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: WASP / WIP / WASP恒常的活性化変異 / WIP欠損症 / X染色体連鎖性好中球減少症

Outline of Final Research Achievements

I showed that all reported constitutively activating mutants of WASP were hyperphosphorylated by Src family tyrosine kinases and demonstrated higher actin polymerization activities compared with wild-type WT WASP. Further analysis showed a tendency of activating WASP mutants to localize in the nucleus compared with WT WASP. ChIP assays revealed that WASP associated with DNA, although the affinity was relatively weaker than RNAP II. To determine whether gene transcription was affected by WASP mutation in myeloid cells, we performed microarray analysis and found different expression profiles between WT and L270P WASP-transfected K562 cells. Among the genes affected, G－CSF receptor, Runx1, and protein tyrosine phosphatase receptor c were included. ChIP on chip analysis of genomic DNA showed WT and L270P WASP had a highly similar DNA-binding pattern but differed in binding affinity at the same locus.

Research Products

• [Journal Article] The open conformation of WASP regulates its nuclear localization and gene transcription in myeloid cells. (2014)
  • Author(s): 2.Looi CY, Sasahara Y, Watanabe Y, Sato M, Hakozaki I, Uchiyama M, Wong WF, Uchiyama T, Kumaki S, Tsuchiya S, Kure S
  • Journal Title: International Immnology Volume: 26 Issue: 6 Pages: 341-352
  • DOI: 10.1093/intimm/dxt072
  • Peer Reviewed / Open Access / Acknowledgement Compliant