共查询到20条相似文献,搜索用时 0 毫秒
1.
《Cell cycle (Georgetown, Tex.)》2013,12(5):647-655
The evolutionarily conserved SWI-SNF chromatin remodeling complex regulates cellular proliferation. A catalytic subunit, BRG-1, is frequently down regulated, silenced or mutated in malignant cells, however, the mechanism by which BRG-1 may function as a tumor suppressor or block breast cancer cellular proliferation is not understood. The cyclin D1 gene is a collaborative oncogene overexpressed in greater than 50% of human breast cancers. Herein, BRG-1 inhibited DNA synthesis and cyclin D1 expression in human MCF-7 breast cancer epithelial cells. The cyclin D1 promoter AP-1 and CRE sites were required for repression by BRG-1 in promoter assays. BRG-1 deficient cells abolished and siRNA to BRG-1 reduced, formation of the BRG-1 chromatin complex. The endogenous cyclin D1 promoter AP-1 site bound BRG-1. Estradiol treatment of MCF7 cells induced recruitment of BRG-1 to the endogenous hpS2 gene promoter. Estradiol, which induced cyclin D1 abundance, was associated with a reduction in recruitment of the co-repressors HP1α/HDAC1 to the endogenous cyclin D1 promoter AP-1/BRG-1 binding sites. These studies suggest the endogenous cyclin D1 promoter BRG-1 binding site functions as a molecular scaffold in the context of local chromatin upon which coactivators and corepressors are recruited to regulate cyclin D1. 相似文献
2.
3.
4.
5.
6.
7.
Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex 总被引:1,自引:0,他引:1
Lin DI Barbash O Kumar KG Weber JD Harper JW Klein-Szanto AJ Rustgi A Fuchs SY Diehl JA 《Molecular cell》2006,24(3):355-366
Growth factor-dependent accumulation of the cyclin D1 proto-oncogene is balanced by its rapid phosphorylation-dependent proteolysis. Degradation is triggered by threonine 286 phosphorylation, which promotes its ubiquitination by an unknown E3 ligase. We demonstrate that Thr286-phosphorylated cyclin D1 is recognized by a Skp1-Cul1-F box (SCF) ubiquitin ligase where FBX4 and alphaB crystallin govern substrate specificity. Overexpression of FBX4 and alphaB crystallin triggered cyclin D1 ubiquitination and increased cyclin D1 turnover. Impairment of SCF(FBX4-alphaB crystallin) function attenuated cyclin D1 ubiquitination, promoting cyclin D1 overexpression and accelerated cell-cycle progression. Purified SCF(FBX4-alphaB crystallin) catalyzed polyubiquitination of cyclin D1 in vitro. Consistent with a putative role for a cyclin D1 E3 ligase in tumorigenesis, FBX4 and alphaB crystallin expression was reduced in tumor-derived cell lines and a subset of primary human cancers that overexpress cyclin D1. We conclude that SCF(FBX4-alphaB crystallin) is an E3 ubiquitin ligase that promotes ubiquitin-dependent degradation of Thr286-phosphorylated cyclin D1. 相似文献
8.
9.
10.
11.
12.
Integration of Rac-dependent regulation of cyclin D1 transcription through a nuclear factor-kappaB-dependent pathway. 总被引:16,自引:0,他引:16
D Joyce B Bouzahzah M Fu C Albanese M D'Amico J Steer J U Klein R J Lee J E Segall J K Westwick C J Der R G Pestell 《The Journal of biological chemistry》1999,274(36):25245-25249
13.
14.
15.
The cyclin D1 gene is transcriptionally repressed by caveolin-1 总被引:11,自引:0,他引:11
Hulit J Bash T Fu M Galbiati F Albanese C Sage DR Schlegel A Zhurinsky J Shtutman M Ben-Ze'ev A Lisanti MP Pestell RG 《The Journal of biological chemistry》2000,275(28):21203-21209
16.
17.
Zhang ZK Davies KP Allen J Zhu L Pestell RG Zagzag D Kalpana GV 《Molecular and cellular biology》2002,22(16):5975-5988
18.
19.