ASPP2 regulates epithelial cell polarity through the PAR complex.
The PAR complex, consisting of the evolutionarily conserved PAR-3, PAR-6, and aPKC, regulates cell polarity in many cell types, including epithelial cells [1-4]. Consistently, genetic manipulation of its components affects tissue integrity in multiple biological systems [5-9]. However, the regulatory mechanisms of the PAR complex remain obscure. We report here that apoptosis-stimulating protein of p53 (ASPP2 or TP53BP2), which binds to the tumor suppressor p53 and stimulates its proapoptotic function [10-12], positively regulates epithelial cell polarity by associating with the PAR complex. ASPP2 interacts and colocalizes with PAR-3 at apical cell-cell junctions in the polarized epithelial cells. Depletion of ASPP2 in epithelial cells causes defects in cell polarity, such as the formation of tight junctions and the maintenance and development of apical membrane domains. Moreover, depletion of ASPP2 causes a defect in PAR-3 localization, as well as vice versa. Furthermore, disturbance in the interaction between ASPP2 and PAR-3 causes defects in cell polarity. We conclude that ASPP2 regulates epithelial cell polarity in cooperation with PAR-3 to form an active PAR complex. Our results, taken together with the known functions of ASPP2, suggest a close relationship between cell polarity and other cell regulatory mechanisms mediated by ASPP2.
Cong
Weili
W
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Japan.
Hirose
Tomonori
T
Harita
Yutaka
Y
Yamashita
Akio
A
Mizuno
Keiko
K
Hirano
Hisashi
H
Ohno
Shigeo
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D051379:Mice; D019108:Tight Junctions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D006023:Glycoproteins; C524369:LGL1 protein, mouse; C115084:Pard3 protein, mouse; C511437:Trp53bp2 protein, mouse; D025521:Tumor Suppressor Proteins