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

• DOI: 10.1093/intimm/dxt072
• Publication Date: 2014-01-09T06:05:25Z
• Authors: Chung Yeng Looi; Yoji Sasahara; Yuko Watanabe; Miki Satoh; Ikuko Hakozaki; Meri Uchiyama; Won Fen Wong; Wei Du; Toru Uchiyama; Satoru Kumaki; Shigeru Tsuchiya; Shigeo Kure
• Keywords: Wiskott–Aldrich syndrome protein

Mutations in the gene encoding Wiskott-Aldrich syndrome protein (WASP) are responsible for and WASP is a major actin regulator cytoplasm. Although rare gain-of-function mutations known to result X-linked neutropenia (XLN), molecular pathogenesis of XLN not fully understood. In this study, we showed that all reported constitutively activating mutants (L270P, S272P I294T) were hyperphosphorylated by Src family tyrosine kinases demonstrated higher polymerization activities compared with wild-type (WT) WASP. Further analysis tendency localize nucleus WT or Y291F mutant addition, found could form complex nuclear RNA-binding protein, 54 kDa (p54nrb) RNA polymerase II (RNAP II). ChIP assays revealed associated DNA, although affinity was relatively weaker than RNAP II. To determine whether transcription affected mutation myeloid cells, performed microarray different expression profiles between L270P WASP-transfected K562 cells. Among genes affected, granulocyte colony-stimulating factor receptor, Runx1, phosphatase receptor c included. on chip genomic DNA had highly similar DNA-binding pattern but differed binding at same locus. Therefore, our results suggest open conformation regulates its localization plays requisite roles regulating would contribute outcome