PMID- 11274402
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20240407
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 7
DP  - 2001 Mar 27
TI  - Inactivation of menin, a Smad3-interacting protein, blocks transforming growth 
      factor type beta signaling.
PG  - 3837-42
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      characterized by endocrine tumors of parathyroids, pancreatic islets, and 
      anterior pituitary. The MEN1 gene encodes a nuclear protein called menin. In MEN1 
      carriers inactivating mutations give rise to a truncated product consistent with 
      menin acting as a tumor suppressor gene. However, the role of menin in 
      tumorigenesis and its physiological functions are not known. Here, we show that 
      menin inactivation by antisense RNA antagonizes transforming growth factor type 
      beta-mediated cell growth inhibition. Menin interacts with Smad3, and antisense 
      menin suppresses transforming growth factor type beta-induced and Smad3-induced 
      transcriptional activity by inhibiting Smad3/4-DNA binding at specific 
      transcriptional regulatory sites. These results implicate a mechanism of 
      tumorigenesis by menin inactivation.
FAU - Kaji, H
AU  - Kaji H
AD  - Calcium Research Laboratory, Royal Victoria Hospital, McGill University, 
      Montreal, QC, Canada H3A 1A1.
FAU - Canaff, L
AU  - Canaff L
FAU - Lebrun, J J
AU  - Lebrun JJ
FAU - Goltzman, D
AU  - Goltzman D
FAU - Hendy, G N
AU  - Hendy GN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010313
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Antisense)
RN  - 0 (SMAD3 protein, human)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, rat)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - CHO Cells
MH  - COS Cells
MH  - Cell Division/drug effects
MH  - Cricetinae
MH  - DNA/drug effects/metabolism
MH  - DNA, Complementary/biosynthesis
MH  - DNA-Binding Proteins/*metabolism/physiology
MH  - Humans
MH  - Neoplasm Proteins/*antagonists & inhibitors/genetics/metabolism
MH  - Pituitary Gland, Anterior/cytology/physiology
MH  - *Proto-Oncogene Proteins
MH  - RNA, Antisense/*pharmacology
MH  - Rats
MH  - Signal Transduction
MH  - Smad3 Protein
MH  - Trans-Activators/*metabolism/physiology
MH  - Transcriptional Activation/drug effects
MH  - Transforming Growth Factor beta/*physiology
MH  - Tumor Cells, Cultured
PMC - PMC31139
EDAT- 2001/03/29 10:00
MHDA- 2001/05/05 10:01
PMCR- 2001/09/27
CRDT- 2001/03/29 10:00
PHST- 2001/03/29 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/03/29 10:00 [entrez]
PHST- 2001/09/27 00:00 [pmc-release]
AID - 061358098 [pii]
AID - 3580 [pii]
AID - 10.1073/pnas.061358098 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3837-42. doi: 10.1073/pnas.061358098. 
      Epub 2001 Mar 13.