Proapoptotic RYBP interacts with FANK1 and induces tumor cell apoptosis through the AP-1 signaling pathway

被引：25

作者：

Ma, Wen ^{[1
,2
,3
]}

Zhang, Xuan ^{[1
,2
]}

Li, Meng ^{[1
,2
]}

Ma, Xiaoli ^{[1
,2
]}

Huang, Bingren ^{[1
,2
]}

Chen, Hong ^{[1
,2
]}

Chen, Deng ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Biochem & Mol Biol, State Key Lab Med Mol Biol, Beijing 100005, Peoples R China

[2] Peking Union Med Coll, Sch Basic Med, Beijing 100005, Peoples R China

[3] Ningxia Peoples Hosp, Dept Lab Med, Ningxia 750002, Peoples R China

来源：

CELLULAR SIGNALLING | 2016年 / 28卷 / 08期

基金：

中国国家自然科学基金;

关键词：

RYBP; FANK1; Protein interaction; Ubiquitination; AP-1; pathway; Apoptosis; TRANSCRIPTION FACTORS; POLYCOMB COMPLEX; PROTEIN RYBP; FIBRONECTIN; EXPRESSION; DOMAIN; YY1; CHEMOTHERAPY; SURVIVAL; TARGETS;

D O I：

10.1016/j.cellsig.2016.03.012

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Ring1 and YY1 Binding Protein (RYBP) induces tumor-specific cell apoptosis, but the underlying molecular mechanism has not been fully understood. Here we conducted a yeast two hybrid screen and identified FANK1 (Fibronectin type HI and ankyrin repeat domains 1) as a novel RYBP-interacting protein. This interaction was confirmed by coimmunoprecipitation, GST pulldown and immunofluorescence assays. We mapped that the FNIII domain at the N-terminal of FANK1 binds to the Serine/Threonine-rich region at the C-terminal of RYBP. Further studies showed that overexpression of RYBP stabilized, whereas knockdown of RYBP by its specific shRNAs reduced, the expression of FANK1. Mechanistic studies revealed that RYBP inhibited the proteasome degradation of polyubiquitinated FANK1, thus prolonging the half-life of FANK1 protein. Functional studies indicated that RYBP activates FANK1-mediated activator protein 1 (AP-1) signaling pathway which contributes to tumor cell apoptosis. Taken together, our current study uncovered a new mechanism which RYBP utilizes to exert its pro-apoptotic activity in human tumor cells. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：779 / 787

页数：9

共 33 条

[1] The Polycomb-associated protein Rybp is a ubiquitin binding protein [J].