The Role of WIP in Wiskott-Aldrich Syndrome

• Published in: The Japanese Journal of Pediatric Hematology Vol. 21; no. 5-6; pp. 217 - 226
• Main Authors: SASAHARA, Yoji, TSUCHIYA, Shigeru
• Format: Journal Article
• Language: Japanese
• Published: THE JAPANESE SOCIETY OF PEDIATRIC HEMATOLOGY/ONCOLOGY 2007; 特定非営利活動法人 日本小児血液・がん学会
• Subjects: immunological synapse; WASP; WIP; Wiskott-Aldrich syndrome
• ISSN: 0913-8706; 1884-4723
• DOI: 10.11412/jjph1987.21.217

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the gene encoding the WAS protein (WASP). WASP is predominantly expressed in hematopoietic cells and regulates the reorganization of actin cytoskeleton in response to cell stimulation including T cell receptor signaling. WASP is localized at the immunological synapses between T cells and antigen-presenting cells. Regulation of WASP functions by its binding molecules, the molecular basis of immunological defects and prediction of clinical outcome in WAS patients have been revealed recently, based on recent basic and clinical research. I have reported the significance of WASP-interacting protein, WIP, as a molecular chaperone for WASP. WIP plays significant roles in the regulation of WASP functions, mechanism of recruitment of WASP to immunological synapses and stability of WASP protein. Protection of WASP by WIP from protein degradation links to the reason why most WASP missense mutations in WAS patients are accumulated in the WIP-binding site. In this article, I review these recent advances, discuss the possibility of an autosomal type of WAS and recent basic approaches to clinical gene therapy for WAS.