共 40 条
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.
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页码:3105 / 3117
页数:13
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