PMID- 21127195
OWN - NLM
STAT- MEDLINE
DCOM- 20110317
LR  - 20220409
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 71
IP  - 2
DP  - 2011 Jan 15
TI  - The tumor suppressor protein menin inhibits AKT activation by regulating its 
      cellular localization.
PG  - 371-82
LID - 10.1158/0008-5472.CAN-10-3221 [doi]
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder 
      associated mainly with tumors of multiple endocrine organs. Mutations in the MEN1 
      gene that encodes for the menin protein are the predominant cause for hereditary 
      MEN1 syndrome. Though menin is a tumor suppressor, its molecular mechanism of 
      action has not been defined. Here, we report that menin interacts with AKT1 in 
      vitro and in vivo. Menin downregulates the level of active AKT and its kinase 
      activity. Through interaction with AKT1, menin suppresses both AKT1-induced 
      proliferation and antiapoptosis in nonendocrine and endocrine cells. Confocal 
      microscopy analysis revealed that menin regulates AKT1 in part by reducing the 
      translocation of AKT1 from the cytoplasm to the plasma membrane during growth 
      factor stimulation. Our findings may be generalizable to other cancers, insofar 
      as we found that loss of menin expression was also associated with AKT activation 
      in a mouse model of pancreatic islet adenoma. Together, our results suggest menin 
      as an important novel negative regulator of AKT kinase activity.
CI  - (c) 2010 AACR.
FAU - Wang, Yan
AU  - Wang Y
AD  - Metabolic Diseases Branch, National Institute of Diabetes and Digestive and 
      Kidney Diseases, NIH, Bethesda, Maryland 20892, USA. wangyan@mail.nih.gov
FAU - Ozawa, Atsushi
AU  - Ozawa A
FAU - Zaman, Shadia
AU  - Zaman S
FAU - Prasad, Nijaguna B
AU  - Prasad NB
FAU - Chandrasekharappa, Settara C
AU  - Chandrasekharappa SC
FAU - Agarwal, Sunita K
AU  - Agarwal SK
FAU - Marx, Stephen J
AU  - Marx SJ
LA  - eng
GR  - Z01 DK043322-01/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20101202
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (MEN1 protein, human)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adenoma, Islet Cell/metabolism
MH  - Animals
MH  - Cell Growth Processes
MH  - Cell Membrane/enzymology/metabolism
MH  - Enzyme Activation
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Microscopy, Confocal
MH  - Pancreatic Neoplasms/metabolism
MH  - Proto-Oncogene Proteins/deficiency/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism
MH  - Transfection
PMC - PMC3076053
MID - NIHMS254298
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2010/12/04 06:00
MHDA- 2011/03/18 06:00
PMCR- 2012/01/15
CRDT- 2010/12/04 06:00
PHST- 2010/12/04 06:00 [entrez]
PHST- 2010/12/04 06:00 [pubmed]
PHST- 2011/03/18 06:00 [medline]
PHST- 2012/01/15 00:00 [pmc-release]
AID - 0008-5472.CAN-10-3221 [pii]
AID - 10.1158/0008-5472.CAN-10-3221 [doi]
PST - ppublish
SO  - Cancer Res. 2011 Jan 15;71(2):371-82. doi: 10.1158/0008-5472.CAN-10-3221. Epub 
      2010 Dec 2.