PMID- 20404349
OWN - NLM
STAT- MEDLINE
DCOM- 20100629
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 24
DP  - 2010 Jun 11
TI  - Regulation of cyclin B2 expression and cell cycle G2/m transition by menin.
PG  - 18291-300
LID - 10.1074/jbc.M110.106575 [doi]
AB  - 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)/M transition. 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.
FAU - Wu, Ting
AU  - Wu T
AD  - Department of Biomedical Sciences, School of Life Science,Medical College, Xiamen 
      University, Xiamen 361005, China.
FAU - Zhang, Xiuli
AU  - Zhang X
FAU - Huang, Xiaohua
AU  - Huang X
FAU - Yang, Yuqing
AU  - Yang Y
FAU - Hua, Xianxin
AU  - Hua X
LA  - eng
GR  - R01-CA-113962/CA/NCI NIH HHS/United States
GR  - R01-CA-100912/CA/NCI NIH HHS/United States
GR  - R01 CA113962/CA/NCI NIH HHS/United States
GR  - R01 CA100912/CA/NCI NIH HHS/United States
GR  - R01 DK097555/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100419
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cyclin B2)
RN  - 0 (Histones)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Cell Proliferation
MH  - Cell Separation
MH  - Cyclin B2/*biosynthesis/metabolism
MH  - Fibroblasts/metabolism
MH  - Flow Cytometry
MH  - G2 Phase
MH  - *Gene Expression Regulation, Neoplastic
MH  - Histones/chemistry
MH  - Mice
MH  - Mutation
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*biosynthesis
MH  - Transcription, Genetic
PMC - PMC2881754
EDAT- 2010/04/21 06:00
MHDA- 2010/06/30 06:00
PMCR- 2011/06/11
CRDT- 2010/04/21 06:00
PHST- 2010/04/21 06:00 [entrez]
PHST- 2010/04/21 06:00 [pubmed]
PHST- 2010/06/30 06:00 [medline]
PHST- 2011/06/11 00:00 [pmc-release]
AID - S0021-9258(19)57537-8 [pii]
AID - M110.106575 [pii]
AID - 10.1074/jbc.M110.106575 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Jun 11;285(24):18291-300. doi: 10.1074/jbc.M110.106575. Epub 
      2010 Apr 19.