Regulation of C1-Ten protein tyrosine phosphatase by p62/SQSTM1-mediated sequestration and degradation.

Ara Koh, Dohyun Park, Heeyoon Jeong, Jiyoun Lee, Mi Nam Lee, Pann-Ghill Suh, Sung Ho Ryu

Cellular signalling 2014 Nov

filter terms:

C1-Ten is a member of the tensin family of focal adhesion molecules but recent studies suggest it plays a more active role in many biological processes because of its potential association with diabetes and cancers. However, relatively little is known about the regulation of C1-Ten, such as changes in its protein level or cellular localization. The cellular localization of C1-Ten is unique because it is expressed in cytoplasmic puncta but nothing is known about these puncta. Here, we show that p62 sequestrates C1-Ten into puncta, making C1-Ten diffuse into the cytoplasm upon p62 depletion. More importantly, p62-mediated C1-Ten sequestration promoted C1-Ten ubiquitination and proteasomal degradation. p62-mediated protein reduction was specific to C1-Ten, and not other tensins such as tensin1 and tensin3. Thus, our results link cellular localization of C1-Ten to an off-switch site for C1-Ten. Additionally, p62 expression increased but C1-Ten protein decreased during muscle differentiation, supporting a role for p62 as a physiological regulator of C1-Ten. Copyright © 2014 Elsevier Inc. All rights reserved.

Citation

Ara Koh, Dohyun Park, Heeyoon Jeong, Jiyoun Lee, Mi Nam Lee, Pann-Ghill Suh, Sung Ho Ryu. Regulation of C1-Ten protein tyrosine phosphatase by p62/SQSTM1-mediated sequestration and degradation. Cellular signalling. 2014 Nov;26(11):2470-80