Polycystin-1 C-terminal tail associates with β-catenin and inhibits canonical Wnt signaling

被引:140
作者
Lal, Mark [1 ]
Song, Xuewen [2 ,3 ]
Pluznick, Jennifer L. [1 ]
Di Giovanni, Valeria [4 ]
Merrick, David M. [1 ]
Rosenblum, Norman D. [4 ,5 ]
Chauvet, Veronique [6 ]
Gottardi, Cara J. [7 ,8 ]
Pei, York [2 ,3 ]
Caplan, Michael J. [1 ]
机构
[1] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA
[2] Univ Toronto, Toronto Gen Hosp, Div Nephrol, Toronto, ON M5G 1L7, Canada
[3] Univ Toronto, Toronto Gen Hosp, Div Genom Med, Toronto, ON M5G 1L7, Canada
[4] Program Dev & Stem Cell Biol, Toronto, ON, Canada
[5] Hosp Sick Children, Div Nephrol, Toronto, ON M5G 1X8, Canada
[6] Inst Curie, UMR 144, Sect Rech, Paris, France
[7] Northwestern Univ, Dept Pulm & Crit Care Med, Chicago, IL 60611 USA
[8] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA
关键词
D O I
10.1093/hmg/ddn208
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Polycystin-1 (PC1), the product of the PKD1 gene mutated in the majority of autosomal dominant polycystic kidney disease (ADPKD) cases, undergoes a cleavage resulting in the intracellular release of its C-terminal tail (CTT). Here, we demonstrate that the PC1 CTT co-localizes with and binds to beta-catenin in the nucleus. This interaction requires a nuclear localization motif present in the PC1 CTT as well as the N-terminal portion of beta-catenin. The PC1 CTT inhibits the ability of both beta-catenin and Wnt ligands to activate T-cell factor (TCF)-dependent gene transcription, a major effector of the canonical Wnt signaling pathway. The PC1 CTT may produce this effect by reducing the apparent affinity of the interaction between beta-catenin and the TCF protein. DNA microarray analysis reveals that the canonical Wnt signaling pathway is activated in ADPKD patient cysts. Our results suggest a novel mechanism through which PC1 cleavage may impact upon Wnt-dependent signaling and thereby modulate both developmental processes and cystogenesis.
引用
收藏
页码:3105 / 3117
页数:13
相关论文
共 40 条
[1]   The polycystic kidney disease 1 gene product mediates protein kinase C α-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1 [J].
Arnould, T ;
Kim, E ;
Tsiokas, L ;
Jochimsen, F ;
Grüning, W ;
Chang, JD ;
Walz, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (11) :6013-6018
[2]   Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling [J].
Bafico, A ;
Gazit, A ;
Pramila, T ;
Finch, PW ;
Yaniv, A ;
Aaronson, SA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (23) :16180-16187
[3]   Polycystin-1 induces cell migration by regulating phosphatidylinositol 3-kinase-dependent cytoskeletal Rearrangements and GSK3β-dependent cell-cell mechanical adhesions [J].
Boca, Manila ;
D'Amato, Lisa ;
Distefano, Gianfranco ;
Polishchuk, Roman S. ;
Germino, Gregory G. ;
Boletta, Alessandra .
MOLECULAR BIOLOGY OF THE CELL, 2007, 18 (10) :4050-4061
[4]   The genetics and physiology of polycystic kidney disease [J].
Calvet, JP ;
Grantham, JJ .
SEMINARS IN NEPHROLOGY, 2001, 21 (02) :107-123
[5]   RETRACTED: β-Catenin N- and C-terminal tails modulate the coordinated binding of adherens junction proteins to β-catenin (Retracted Article) [J].
Castaño, J ;
Raurell, I ;
Piedra, JA ;
Miravet, S ;
Duñach, M ;
de Herreros, AG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (35) :31541-31550
[6]   Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus [J].
Chauvet, V ;
Tian, X ;
Husson, H ;
Grimm, DH ;
Wang, T ;
Hieseberger, T ;
Igarashi, P ;
Bennett, AM ;
Ibraghimov-Beskrovnaya, O ;
Somlo, S ;
Caplan, MJ .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (10) :1433-1443
[7]   ELEVATED C-MYC PROTOONCOGENE EXPRESSION IN AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY-DISEASE [J].
COWLEY, BD ;
SMARDO, FL ;
GRANTHAM, JJ ;
CALVET, JP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8394-8398
[8]   Distinct molecular forms of β-catenin are targeted to adhesive or transcriptional complexes [J].
Gottardi, CJ ;
Gumbiner, BM .
JOURNAL OF CELL BIOLOGY, 2004, 167 (02) :339-349
[9]   Adhesion signaling:: How β-catenin interacts with its partners [J].
Gottardi, CJ ;
Gumbiner, BM .
CURRENT BIOLOGY, 2001, 11 (19) :R792-R794
[10]   CYST FORMATION AND GROWTH IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY-DISEASE [J].
GRANTHAM, JJ ;
GEISER, JL ;
EVAN, AP .
KIDNEY INTERNATIONAL, 1987, 31 (05) :1145-1152