PMID- 17024155
OWN - NLM
STAT- MEDLINE
DCOM- 20061114
LR  - 20181201
IS  - 1745-8366 (Print)
IS  - 1745-8366 (Linking)
VI  - 2
IP  - 10
DP  - 2006 Oct
TI  - Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin 
      modifications and transcription regulation.
PG  - 562-70
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome 
      characterized by tumors of the parathyroid glands, the pancreatic islets, the 
      pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid 
      tumors, often at a young age. Causal to the syndrome are germline mutations of 
      the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has 
      enabled presymptomatic diagnosis and treatment of MEN1-related lesions. The 
      product of the MEN1 gene is the nuclear protein menin. Recent observations 
      indicate several functions for menin in the regulation of transcription, serving 
      either as a repressor or as an activator: menin interacts with the 
      activator-protein-1-family transcription factor JunD, changing it from an 
      oncoprotein into a tumor-suppressor protein, putatively by recruitment of histone 
      deacetylase complexes; menin maintains transforming growth factor beta mediated 
      signal transduction involved in parathyroid hormone and prolactin gene 
      expression; and menin is an integral component of histone methyltransferase 
      complexes. In this capacity menin is a regulator of expression of the 
      cyclin-dependent-kinase inhibitors p18INK4C and p27Kip1; furthermore, menin 
      serves as a co-activator of estrogen receptor mediated transcription, by 
      recruiting methyltransferase activity to lysine 4 of histone 3 at the estrogen 
      responsive TFF1(pS2) gene promoter. We propose that menin links 
      transcription-factor function to histone-modification pathways and that this is 
      crucial for MEN1 tumorigenesis. Understanding the molecular pathology of MEN1 
      tumorigenesis will lead to new therapeutic strategies.
FAU - Dreijerink, Koen Ma
AU  - Dreijerink KM
AD  - Department of Internal Medicine and Endocrinology, University Medical Center 
      Utrecht, The Netherlands.
FAU - Hoppener, Jo Wm
AU  - Hoppener JW
FAU - Timmers, Ht Marc
AU  - Timmers HM
FAU - Lips, Cornelis Jm
AU  - Lips CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Nat Clin Pract Endocrinol Metab
JT  - Nature clinical practice. Endocrinology & metabolism
JID - 101261798
RN  - 0 (Chromatin)
RN  - 0 (MEN1 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.- (Protein Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
SB  - IM
MH  - Animals
MH  - Cell Nucleolus/metabolism
MH  - Chromatin/*metabolism
MH  - *Gene Expression Regulation
MH  - Genes, jun/physiology
MH  - Histone Methyltransferases
MH  - Histone-Lysine N-Methyltransferase/physiology
MH  - Humans
MH  - Models, Biological
MH  - Multiple Endocrine Neoplasia Type 1/diagnosis/*genetics
MH  - NF-kappa B/physiology
MH  - Protein Methyltransferases
MH  - Proto-Oncogene Proteins/genetics/metabolism/*physiology
MH  - Signal Transduction
MH  - *Transcription, Genetic
MH  - Transforming Growth Factor beta/physiology
RF  - 50
EDAT- 2006/10/07 09:00
MHDA- 2006/11/15 09:00
CRDT- 2006/10/07 09:00
PHST- 2005/12/16 00:00 [received]
PHST- 2006/04/27 00:00 [accepted]
PHST- 2006/10/07 09:00 [pubmed]
PHST- 2006/11/15 09:00 [medline]
PHST- 2006/10/07 09:00 [entrez]
AID - ncpendmet0292 [pii]
AID - 10.1038/ncpendmet0292 [doi]
PST - ppublish
SO  - Nat Clin Pract Endocrinol Metab. 2006 Oct;2(10):562-70. doi: 
      10.1038/ncpendmet0292.