PMID- 10500243
OWN - NLM
STAT- MEDLINE
DCOM- 19991105
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1447
IP  - 1
DP  - 1999 Oct 6
TI  - Menin represses JunD-activated transcription by a histone deacetylase-dependent 
      mechanism.
PG  - 51-6
AB  - Recently the multiple endocrine neoplasia type 1 (MEN-1) tumor suppressor gene 
      was cloned. MEN-1 encodes a nuclear protein, called menin, of hitherto unknown 
      function. In order to investigate the biological function of menin we employed 
      the yeast two-hybrid system to identify menin-interacting proteins. Here we 
      report that menin functions as a transcriptional repressor through interaction 
      with the transcription factor JunD. The interaction is mediated via the 
      N-terminal transcription activation domain of JunD, and the C-terminal part of 
      menin. In transient co-transfection experiments, expression of menin leads to 
      specific repression of JunD transcriptional activity, which is dependent on the 
      integrity of the menin C-terminal region. C-Terminal truncations of the protein 
      not only abolish repression, but increase JunD transcriptional activity, implying 
      the existence of a functional domain separate from the JunD-binding region. 
      Menin-mediated repression is relieved by the histone deacetylase inhibitor 
      trichostatin A, indicating that deacetylation of histones is an essential 
      component of this repression mechanism, as has recently been demonstrated for the 
      retinoblastoma protein. Missense, in-frame deletions, frameshift and nonsense 
      mutations lead to inactivation of menin or possibly to truncated proteins. This 
      would result in loss of repression of menin/JunD target genes, as well as 
      non-target genes through indirect mechanisms, deregulation of cellular growth 
      control and endocrine tumorigenesis.
FAU - Gobl, A E
AU  - Gobl AE
AD  - Department of Medical Sciences, Endocrine Oncology Unit, Uppsala University 
      Hospital, S-751 85, Uppsala, Sweden. anders.gobl@medicin.uu.se
FAU - Berg, M
AU  - Berg M
FAU - Lopez-Egido, J R
AU  - Lopez-Egido JR
FAU - Oberg, K
AU  - Oberg K
FAU - Skogseid, B
AU  - Skogseid B
FAU - Westin, G
AU  - Westin G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Down-Regulation
MH  - Gene Library
MH  - Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/*metabolism
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Luciferases
MH  - Multiple Endocrine Neoplasia Type 1/genetics
MH  - Mutation
MH  - Neoplasm Proteins/*genetics/pharmacology
MH  - Protein Binding
MH  - *Proto-Oncogene Proteins
MH  - Proto-Oncogene Proteins c-jun/*pharmacology
MH  - Transcriptional Activation/*drug effects
MH  - Transfection
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - S0167-4781(99)00132-3 [pii]
AID - 10.1016/s0167-4781(99)00132-3 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1999 Oct 6;1447(1):51-6. doi: 
      10.1016/s0167-4781(99)00132-3.