title: WIP remodeling actin behind the scenes: how WIP reshapes immune and other functions.
abstract: Actin polymerization is a fundamental cellular process regulating immune cell functions and the immune response. The Wiskott-Aldrich syndrome protein (WASp) is an actin nucleation promoting factor, which is exclusively expressed in hematopoietic cells, where it plays a key regulatory role in cytoskeletal dynamics. WASp interacting protein (WIP) was first discovered as the binding partner of WASp, through the use of the yeast two hybrid system. WIP was later identified as a chaperone of WASp, necessary for its stability. Mutations occurring at the WASp homology 1 domain (WH1), which serves as the WIP binding site, were found to cause the Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). WAS manifests as an immune deficiency characterized by eczema, thrombocytopenia, recurrent infections, and hematopoietic malignancies, demonstrating the importance of WIP for WASp complex formation and for a proper immune response. WIP deficiency was found to lead to different abnormalities in the activity of various lymphocytes, suggesting differential cell-dependent roles for WIP. Additionally, WIP deficiency causes cellular abnormalities not found in WASp-deficient cells, indicating that WIP fulfills roles beyond stabilizing WASp. Indeed, WIP was shown to interact with various binding partners, including the signaling proteins Nck, CrkL and cortactin. Recent studies have demonstrated that WIP also takes part in non immune cellular processes such as cancer invasion and metastasis, in addition to cell subversion by intracellular pathogens. Understanding of numerous functions of WIP can enhance our current understanding of activation and function of immune and other cell types.
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors: Elad
authors: E
authors: Noy
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors: Sophia
authors: S
authors: Fried
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors: Omri
authors: O
authors: Matalon
authors: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors: Mira
authors: M
authors: Barda-Saad
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000818:Animals; D051356:Cortactin / Q000235:genetics / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology*; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D015513:Oncogene Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013921:Thrombocytopenia / Q000235:genetics / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000276:immunology; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000276:immunology
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; C495868:CTTN protein, human; D051356:Cortactin; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C078332:Nck protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C495767:WAS protein, human; C109903:WIPF1 protein, human; D051316:Wiskott-Aldrich Syndrome Protein