TY - JOUR
T1 - Ubiquitylation-dependent negative regulation of wasp is essential for actin cytoskeleton dynamics
AU - Reicher, Barak
AU - Joseph, Noah
AU - David, Ahuvit
AU - Pauker, Maor H.
AU - Perl, Orly
AU - Barda-Saad, Mira
N1 - 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).
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864585880&partnerID=8YFLogxK
U2 - 10.1128/MCB.00161-12
DO - 10.1128/MCB.00161-12
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C2 - 22665495
AN - SCOPUS:84864585880
SN - 0270-7306
VL - 32
SP - 3153
EP - 3163
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 15
ER -