Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribos...Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribosomal functions of RPs are rarely reported. Herein, we identified a ribosomal protein S7-interacting partner, BCCIPβ, which modulates the functional conversion of S7. Through the N-terminal acidic domain, BCCIPβ interacts with the central basic region in S7 and regulates the extraribosomal dis- tribution of S7. BCCIPI~ deficiency abrogates the ribosomal accumulation but enhances the ribosome-free location of S7. This translocation further impairs protein synthesis and triggers ribosomal stress. Consequently, BCCIPβ deficiency suppresses the ribosomal function and initiates the extraribosomal function of S7, resulting in restriction of cell proliferation. Moreover, clinically relevant S7 mutations were found to dampen the interaction with BCCIPβ and facilitate the functional transition of S7. In conclu- sion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomai functions of S7 and has implica- tions in cell growth and tumor development.展开更多
The BCCIP （BRCA2. and CDKNIA-interacting protein） is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCClP is observed in multiple clinically diagnosed primary tumor tissues such...The BCCIP （BRCA2. and CDKNIA-interacting protein） is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCClP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and col- orectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 sub- units catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCClP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation （CHIP） experiments clarify the enrichment of INO80 and YY1 at ＋0.17 kb downstream of the BCClP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCClP promoter region. Our findings strongly indicate that BCClP is a potential target gene of the INO80/YY1 complex.展开更多
BCCIP(BRCA2 and CDKN1A interacting protein)是一个与BRCA2和CDKN1A(p21)相互作用的蛋白,其多个结构域在进化上高度保守,提示BCCIP生物学功能的重要性。BCCIP在细胞内通过与BRCA2和RAD51相互作用参与DNA损伤修复并维持基因组稳定性;...BCCIP(BRCA2 and CDKN1A interacting protein)是一个与BRCA2和CDKN1A(p21)相互作用的蛋白,其多个结构域在进化上高度保守,提示BCCIP生物学功能的重要性。BCCIP在细胞内通过与BRCA2和RAD51相互作用参与DNA损伤修复并维持基因组稳定性;通过和p21相互作用使细胞阻滞于G1/S期;通过参与微管和纺锤体形成而影响细胞分裂等;在BCCIP敲除小鼠的乳腺中可形成良性肿瘤或恶性肿瘤,提示BCCIP是一个重要的抑癌基因,可能成为相关肿瘤的诊断标志物和治疗靶点。本文就肿瘤抑制因子BCCIP作用的研究进展作一综述。展开更多
文摘Extraribosomal functions of ribosomal proteins （RPs） have gained much attention for their implications in tumorigenesis and pro- gression. However, the regulations for transition between the ribosomal and extraribosomal functions of RPs are rarely reported. Herein, we identified a ribosomal protein S7-interacting partner, BCCIPβ, which modulates the functional conversion of S7. Through the N-terminal acidic domain, BCCIPβ interacts with the central basic region in S7 and regulates the extraribosomal dis- tribution of S7. BCCIPI~ deficiency abrogates the ribosomal accumulation but enhances the ribosome-free location of S7. This translocation further impairs protein synthesis and triggers ribosomal stress. Consequently, BCCIPβ deficiency suppresses the ribosomal function and initiates the extraribosomal function of S7, resulting in restriction of cell proliferation. Moreover, clinically relevant S7 mutations were found to dampen the interaction with BCCIPβ and facilitate the functional transition of S7. In conclu- sion, BCCIPβ, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomai functions of S7 and has implica- tions in cell growth and tumor development.
基金This work was supported by the National Natural Science Foundation of China （Grant Nos. 31071131 and 31171245）, by the National Laboratory of Biomacromolecules （O5SY02110A and 2012kf04）, and by the Project of Jilin Province Science and Technology Development Program （20130413002GH）.
文摘The BCCIP （BRCA2. and CDKNIA-interacting protein） is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCClP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and col- orectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 sub- units catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCClP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation （CHIP） experiments clarify the enrichment of INO80 and YY1 at ＋0.17 kb downstream of the BCClP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCClP promoter region. Our findings strongly indicate that BCClP is a potential target gene of the INO80/YY1 complex.
文摘BCCIP(BRCA2 and CDKN1A interacting protein)是一个与BRCA2和CDKN1A(p21)相互作用的蛋白,其多个结构域在进化上高度保守,提示BCCIP生物学功能的重要性。BCCIP在细胞内通过与BRCA2和RAD51相互作用参与DNA损伤修复并维持基因组稳定性;通过和p21相互作用使细胞阻滞于G1/S期;通过参与微管和纺锤体形成而影响细胞分裂等;在BCCIP敲除小鼠的乳腺中可形成良性肿瘤或恶性肿瘤,提示BCCIP是一个重要的抑癌基因,可能成为相关肿瘤的诊断标志物和治疗靶点。本文就肿瘤抑制因子BCCIP作用的研究进展作一综述。
