PMID- 17016429
OWN - NLM
STAT- MEDLINE
DCOM- 20070917
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 26
IP  - 16
DP  - 2007 Apr 5
TI  - Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in 
      response to DNA damage.
PG  - 2283-9
AB  - We discovered a novel oncogene in a T-cell lymphoma cell line, multiple copies in 
      T-cell lymphoma-1 (MCT-1), that has been shown to decrease cell-doubling time, 
      shorten the duration of G(1) transit time and/or G(1)-S transition, and transform 
      NIH3T3 fibroblasts. We subsequently demonstrated that there were significantly 
      increased levels of MCT-1 protein in a subset of primary diffuse large B-cell 
      lymphomas. Levels of MCT-1 protein were shown to be increased after exposure to 
      DNA damaging agents. This increase did not require new protein synthesis, 
      suggesting that post-translational mechanisms were involved. Phosphorylation is 
      one potential mechanism by which the activity of molecules involved in cell 
      cycle/survival is rapidly modulated. The 
      RAS/mitogen-activated/extracellular-regulated kinase (MEK)/extracellular 
      signal-regulated kinases (ERK) pathway plays a prominent role in the regulation 
      of cell growth and proliferation through phosphorylation-dependent regulation of 
      several substrates. The MCT-1 protein is predicted to have numerous putative 
      phosphorylation sites. Using a combination of genetic and pharmacological 
      approaches, we established that phosphorylation of MCT-1 protein by p44/p42 
      mitogen-activated protein kinases is critical for stabilization of MCT-1 protein 
      and for its ability to promote cell proliferation. Our data suggests that 
      targeting the RAS/MEK/ERK signal transduction cascade may provide a potential 
      therapeutic approach in lymphomas and related malignancies that exhibit high 
      levels of MCT-1 protein.
FAU - Nandi, S
AU  - Nandi S
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
FAU - Reinert, L S
AU  - Reinert LS
FAU - Hachem, A
AU  - Hachem A
FAU - Mazan-Mamczarz, K
AU  - Mazan-Mamczarz K
FAU - Hagner, P
AU  - Hagner P
FAU - He, H
AU  - He H
FAU - Gartenhaus, R B
AU  - Gartenhaus RB
LA  - eng
PT  - Journal Article
DEP - 20061002
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (MCTS1 protein, human)
RN  - 0 (Oncogene Proteins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Cycle
MH  - Cell Cycle Proteins/chemistry/genetics/*metabolism
MH  - Cell Division
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - *DNA Damage
MH  - Humans
MH  - Jurkat Cells
MH  - Kinetics
MH  - Lymphoma, T-Cell/genetics/pathology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Molecular Sequence Data
MH  - Oncogene Proteins/chemistry/genetics/*metabolism
MH  - Phosphorylation
EDAT- 2006/10/04 09:00
MHDA- 2007/09/18 09:00
CRDT- 2006/10/04 09:00
PHST- 2006/10/04 09:00 [pubmed]
PHST- 2007/09/18 09:00 [medline]
PHST- 2006/10/04 09:00 [entrez]
AID - 1210030 [pii]
AID - 10.1038/sj.onc.1210030 [doi]
PST - ppublish
SO  - Oncogene. 2007 Apr 5;26(16):2283-9. doi: 10.1038/sj.onc.1210030. Epub 2006 Oct 2.