title: Regulation of C1-Ten protein tyrosine phosphatase by p62/SQSTM1-mediated sequestration and degradation.
abstract: 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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Ara
authors.initials: A
authors.lastname: Koh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Heeyoon
authors.initials: H
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea.
authors.forename: Mi Nam
authors.initials: MN
authors.lastname: Lee
authors.affiliation: School of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan 689-798, South Korea.
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang 790-784, South Korea. Electronic address: sungho@postech.ac.kr.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D000071456:Sequestosome-1 Protein; D000070876:Tensins; D054875:Ubiquitination / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008840:Microfilament Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C000603369:TNS1 protein, human; C000603370:TNS3 protein, human; D000070876:Tensins; C452816:TNS2 protein, human; D010744:Phosphoric Monoester Hydrolases; D046988:Proteasome Endopeptidase Complex
keywords: C1-Ten; Degradation; Sequestosome; Tensin2; p62