Ubiquitylation-dependent negative regulation of wasp is essential for actin cytoskeleton dynamics

Barak Reicher, Noah Joseph, Ahuvit David, Maor H. Pauker, Orly Perl, Mira Barda-Saad

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


The Wiskott-Aldrich syndrome protein (WASp) is a key regulator of actin dynamics during cell motility and adhesion, and mutations in its gene are responsible for Wiskott-Aldrich syndrome (WAS). Here, we demonstrate that WASp is ubiquitylated following T-cell antigen receptor (TCR) activation. WASp phosphorylation at tyrosine 291 results in recruitment of the E3 ligase Cbl-b, which, together with c-Cbl, carries out WASp ubiquitylation. Lysine residues 76 and 81, located at the WASp WH1 domain, which contains the vast majority of WASp gene mutations, serve as the ubiquitylation sites. Disruption of WASp ubiquitylation causes WASp accumulation and alters actin dynamics and the formation of actin-dependent structures. Our data suggest that regulated degradation of activated WASp might be an efficient strategy by which the duration and localization of actin rearrangement and the intensity of T-cell activation are controlled.

Original languageEnglish
Pages (from-to)3153-3163
Number of pages11
JournalMolecular and Cellular Biology
Issue number15
StatePublished - Aug 2012

Bibliographical note

This research was funded by the Israel Cancer Association through the estate of the late Alexander Smidoda, the Israeli Ministry of Health through the Office of the Chief Scientist, and by the Israel Science Foundation (grant numbers 1659/08, 971/08, and 491/10).


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