Regulation of Cyclin B2 Expression and Cell Cycle G(2)/M Transition by Menin

CORC > 厦门大学 > 化学化工－已发表论文

	Regulation of Cyclin B2 Expression and Cell Cycle G(2)/M Transition by Menin
	Wu, T ; Zhang, XL ; Huang, XH ; Yang, YQ ; Hua, XX
刊名	http://dx.doi.org/10.1074/jbc.M110.106575
	2010-06-11
关键词	TUMOR-SUPPRESSOR MENIN MITOSIS-SPECIFIC PHOSPHORYLATION MITOTIC CHROMOSOME CONDENSATION JUND-ACTIVATED TRANSCRIPTION ENDOCRINE NEOPLASIA TYPE-1 GENE-EXPRESSION HISTONE H3 NF-Y DNA-REPLICATION PROTEIN-KINASE
英文摘要	National Institutes of Health [R01-CA-100912, R01-CA-113962]; American Diabetes Association [7-07-RA-60]; Multiple endocrine neoplasia type 1 (MEN1) results from mutations in tumor suppressor gene Men1, which encodes nuclear protein menin. Menin up-regulates certain cyclin-dependent kinase inhibitors through increasing histone H3 lysine 4 (H3K4) methylation and inhibits G(0)/G(1) to S phase transition. However, little is known as to whether menin controls G(2)/M-phase transition, another important cell cycle checkpoint. Here, we show that menin expression delays G(2)/M phase transition and reduces expression of Ccnb2 (encoding cyclin B2). Menin associates with the promoter of Ccnb2 and reduces histone H3 acetylation, a positive chromatin marker for gene transcription, at the Ccnb2 locus. Moreover, Men1 ablation leads to an increase in cyclin B2 expression, histone H3 acetylation at the Ccnb2 locus, and G(2)/Mtransition. In contrast, knockdown of cyclin B2 diminishes the number of cells at M phase and reduces cell proliferation. Furthermore, menin interferes with binding of certain positive transcriptional regulators, such as nuclear factor Y (NF-Y), E2 factors (E2Fs), and histone acetyltransferase CREB (cAMP-response element-binding protein)binding protein (CBP) to the Ccnb2 locus. Notably, MEN1 disease-related mutations, A242V and L22R, abrogate the ability of menin to repress cyclin B2 expression and G(2)/M transition. Both of the mutants fail to reduce the acetylated level of the Ccnb2 locus. Together, these results suggest that menin-mediated repression of cyclin B2 is crucial for inhibiting G(2)/M transition and cell proliferation through a previously unrecognized molecular mechanism for menin-induced suppression of MEN1 tumorigenesis.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/62376]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Wu, T,Zhang, XL,Huang, XH,et al. Regulation of Cyclin B2 Expression and Cell Cycle G(2)/M Transition by Menin[J]. http://dx.doi.org/10.1074/jbc.M110.106575,2010.
APA	Wu, T,Zhang, XL,Huang, XH,Yang, YQ,&Hua, XX.(2010).Regulation of Cyclin B2 Expression and Cell Cycle G(2)/M Transition by Menin.http://dx.doi.org/10.1074/jbc.M110.106575.
MLA	Wu, T,et al."Regulation of Cyclin B2 Expression and Cell Cycle G(2)/M Transition by Menin".http://dx.doi.org/10.1074/jbc.M110.106575 (2010).