PMID- 17766243
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 43
DP  - 2007 Oct 26
TI  - Menin-mediated caspase 8 expression in suppressing multiple endocrine neoplasia 
      type 1.
PG  - 31332-40
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a familial tumor syndrome linked to 
      mutation of the MEN1 gene, which encodes a tumor suppressor, menin. We previously 
      reported that menin up-regulates the caspase 8 expression and promotes 
      TNF-alpha-induced apoptosis. However, it remains unclear how menin up-regulates 
      caspase 8 expression and whether menin-mediated caspase 8 expression plays a role 
      in repressing MEN1 development. Here we show that menin binds the 5'-untranslated 
      region (5'-UTR) of the Caspase 8 locus in vivo and activates transcription of a 
      reporter gene through the 5'-UTR. Menin directly binds the 5'-UTR in a 
      sequence-independent manner in vitro. Moreover, Men1 ablation in cells reduces 
      acetylation of histones H3 and H4 at the 5'-UTR of the caspase 8 locus bound by 
      menin in vivo. Notably, the MEN1-derived menin point mutants lose their ability 
      to bind the caspase 8 locus and fail to induce caspase 8 expression and 
      TNF-alpha-mediated apoptosis. Consistent with these observations, the expression 
      level of caspase 8 is markedly reduced in insulinomas from Men1(+/-) mice. 
      Together, our results indicate that menin enhances the caspase 8 expression by 
      binding the caspase 8 locus, and suggest that menin suppresses MEN1 
      tumorigenesis, at least in part, by up-regulating caspase 8 expression.
FAU - La, Ping
AU  - La P
AD  - Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson 
      Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, 
      USA.
FAU - Yang, Yuqing
AU  - Yang Y
FAU - Karnik, Satyajit K
AU  - Karnik SK
FAU - Silva, Albert C
AU  - Silva AC
FAU - Schnepp, Robert W
AU  - Schnepp RW
FAU - Kim, Seung K
AU  - Kim SK
FAU - Hua, Xianxin
AU  - Hua X
LA  - eng
GR  - R01 CA100912/CA/NCI NIH HHS/United States
GR  - R01 CA100912-04/CA/NCI NIH HHS/United States
GR  - R01 CA113962/CA/NCI NIH HHS/United States
GR  - R01 CA113962-04/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070831
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (5' Untranslated Regions)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - 5' Untranslated Regions/metabolism
MH  - Animals
MH  - Caspase 8/*metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chromatin Immunoprecipitation
MH  - Embryo, Mammalian/cytology
MH  - Escherichia coli/genetics
MH  - Fibroblasts/metabolism
MH  - Genes, Reporter
MH  - Heterozygote
MH  - Humans
MH  - Insulinoma/metabolism/*pathology
MH  - Kidney/cytology
MH  - Luciferases/metabolism
MH  - Mice
MH  - Multiple Endocrine Neoplasia Type 1/*metabolism
MH  - Plasmids
MH  - Point Mutation
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Retroviridae/genetics
MH  - Transfection
PMC - PMC2858561
MID - NIHMS183848
EDAT- 2007/09/04 09:00
MHDA- 2007/12/07 09:00
PMCR- 2010/04/22
CRDT- 2007/09/04 09:00
PHST- 2007/09/04 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/09/04 09:00 [entrez]
PHST- 2010/04/22 00:00 [pmc-release]
AID - S0021-9258(20)68656-2 [pii]
AID - 10.1074/jbc.M609555200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Oct 26;282(43):31332-40. doi: 10.1074/jbc.M609555200. Epub 2007 
      Aug 31.