PMID- 15640349
OWN - NLM
STAT- MEDLINE
DCOM- 20050315
LR  - 20190816
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 102
IP  - 3
DP  - 2005 Jan 18
TI  - Menin and MLL cooperatively regulate expression of cyclin-dependent kinase 
      inhibitors.
PG  - 749-54
AB  - Mutations in the MEN1 gene are associated with the multiple endocrine neoplasia 
      syndrome type 1 (MEN1), which is characterized by parathyroid hyperplasia and 
      tumors of the pituitary and pancreatic islets. The mechanism by which MEN1 acts 
      as a tumor suppressor is unclear. We have recently shown that menin, the MEN1 
      protein product, interacts with mixed lineage leukemia (MLL) family proteins in a 
      histone methyltransferase complex including Ash2, Rbbp5, and WDR5. Here, we show 
      that menin directly regulates expression of the cyclin-dependent kinase 
      inhibitors p27Kip1 and p18Ink4c. Menin activates transcription by means of a 
      mechanism involving recruitment of MLL to the p27Kip1 and p18Ink4c promoters and 
      coding regions. Loss of function of either MLL or menin results in 
      down-regulation of p27Kip1 and p18Ink4c expression and deregulated cell growth. 
      These findings suggest that regulation of cyclin-dependent kinase inhibitor 
      transcription by cooperative interaction between menin and MLL plays a central 
      role in menin's activity as a tumor suppressor.
FAU - Milne, Thomas A
AU  - Milne TA
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania 
      School of Medicine, Philadelphia, PA 19104, USA.
FAU - Hughes, Christina M
AU  - Hughes CM
FAU - Lloyd, Ricardo
AU  - Lloyd R
FAU - Yang, Zhaohai
AU  - Yang Z
FAU - Rozenblatt-Rosen, Orit
AU  - Rozenblatt-Rosen O
FAU - Dou, Yali
AU  - Dou Y
FAU - Schnepp, Robert W
AU  - Schnepp RW
FAU - Krankel, Cynthia
AU  - Krankel C
FAU - Livolsi, Virginia A
AU  - Livolsi VA
FAU - Gibbs, Denise
AU  - Gibbs D
FAU - Hua, Xianxin
AU  - Hua X
FAU - Roeder, Robert G
AU  - Roeder RG
FAU - Meyerson, Matthew
AU  - Meyerson M
FAU - Hess, Jay L
AU  - Hess JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050107
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 (CDKN1B protein, human)
RN  - 0 (CDKN2C protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p18)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KMT2A protein, human)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Carrier Proteins/genetics
MH  - Cell Cycle Proteins/genetics
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cyclin-Dependent Kinase Inhibitor p18
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclin-Dependent Kinases/*antagonists & inhibitors
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - *Gene Expression Regulation
MH  - Histone-Lysine N-Methyltransferase
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Myeloid-Lymphoid Leukemia Protein
MH  - Open Reading Frames
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*physiology
MH  - Proto-Oncogenes/genetics/*physiology
MH  - Transcription Factors/genetics/*physiology
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Suppressor Proteins/genetics
PMC - PMC545577
EDAT- 2005/01/11 09:00
MHDA- 2005/03/16 09:00
PMCR- 2005/07/18
CRDT- 2005/01/11 09:00
PHST- 2005/01/11 09:00 [pubmed]
PHST- 2005/03/16 09:00 [medline]
PHST- 2005/01/11 09:00 [entrez]
PHST- 2005/07/18 00:00 [pmc-release]
AID - 0408836102 [pii]
AID - 01020749 [pii]
AID - 10.1073/pnas.0408836102 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):749-54. doi: 
      10.1073/pnas.0408836102. Epub 2005 Jan 7.