PMID- 16449969
OWN - NLM
STAT- MEDLINE
DCOM- 20060803
LR  - 20081121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 25
IP  - 25
DP  - 2006 Jun 15
TI  - Tumor suppressor menin: the essential role of nuclear localization signal domains 
      in coordinating gene expression.
PG  - 3537-46
AB  - Menin is encoded by the tumor suppressor gene MEN1 that is mutated in patients 
      with an inherited tumor syndrome, multiple endocrine neoplasia type 1 (MEN1). 
      Although menin is a nuclear protein and directly binds to DNA through its nuclear 
      localization signals (NLSs), the precise role for each of the NLSs in nuclear 
      translocation and gene expression remains to be elucidated. Here, we show that 
      point mutations in three individual NLSs, NLS1, NLS2, and a novel accessory NLS, 
      NLSa, do not block nuclear translocation, but compromise the ability of menin to 
      repress expression of the endogenous insulin-like growth factor binding protein-2 
      (IGFBP-2) gene. This repression is not released by an inhibitor of histone 
      deacetylases. Although subtle mutations in menin NLSs do not affect menin 
      association with chromatin, they abolish menin binding to the IGFBP-2 promoter in 
      vivo. Furthermore, each of the NLSs is also crucial for menin-mediated induction 
      of caspase 8 expression. Together, these results suggest that menin may act as a 
      scaffold protein in coordinating activation and repression of gene transcription 
      and that its NLSs play a more important role in controlling gene transcription 
      than merely targeting menin into the nucleus.
FAU - La, P
AU  - La P
AD  - Department of Cancer Biology, Abramson Family Cancer Research Institute, Abramson 
      Cancer Center, University of Pennsylvania, Philadelphia, USA.
FAU - Desmond, A
AU  - Desmond A
FAU - Hou, Z
AU  - Hou Z
FAU - Silva, A C
AU  - Silva AC
FAU - Schnepp, R W
AU  - Schnepp RW
FAU - Hua, X
AU  - Hua X
LA  - eng
GR  - R01 CA100912/CA/NCI NIH HHS/United States
GR  - R01 CA113962/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060130
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Insulin-Like Growth Factor Binding Protein 2)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Blotting, Western
MH  - Caspase 8
MH  - Caspases/metabolism
MH  - Cell Line
MH  - Fluorescent Antibody Technique
MH  - Gene Expression
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Protein 2/metabolism
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Localization Signals/*genetics/*metabolism
MH  - Point Mutation
MH  - Promoter Regions, Genetic
MH  - Protein Transport/genetics
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Homology, Amino Acid
MH  - *Transcription, Genetic
EDAT- 2006/02/02 09:00
MHDA- 2006/08/04 09:00
CRDT- 2006/02/02 09:00
PHST- 2006/02/02 09:00 [pubmed]
PHST- 2006/08/04 09:00 [medline]
PHST- 2006/02/02 09:00 [entrez]
AID - 1209400 [pii]
AID - 10.1038/sj.onc.1209400 [doi]
PST - ppublish
SO  - Oncogene. 2006 Jun 15;25(25):3537-46. doi: 10.1038/sj.onc.1209400. Epub 2006 Jan 
      30.