PMID- 10523842
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 41
DP  - 1999 Oct 7
TI  - Role of two upstream open reading frames in the translational control of oncogene
      mdm2.
PG  - 5631-7
AB  - Overexpression of oncoprotein MDM2 has been found in a significant number of
      human soft tissue tumors. In a subset of these tumors, overexpression is a result
      of enhanced translation of mdm2 mRNA. There are two transcripts from the mdm2
      gene that differ only in their 5' leaders: a long form (L-mdm2) and a short form 
      (S-mdm2) that arise from the use of different promoters. L-mdm2 mRNA contains two
      upstream open reading frames (uORFs) and this mRNA was loaded with ribosomes
      inefficiently in comparison with S-mdm2. The 5' leader of L-mdm2 was sufficient
      to transfer translational repression to a reporter gene and the two uORFs acted
      synergistically to achieve full suppression. In contrast, the 5' leader of S-mdm2
      allowed efficient translation of an attached reporter gene in the tumor cells.
      These results are consistent with a model in which overexpression of MDM2 in
      certain tumors results from a change in mRNA structure due to a switch in
      promoter usage.
FAU - Brown, C Y
AU  - Brown CY
AD  - Department of Biochemistry, University of Washington, Seattle, Washington, WA
      98195-7350, USA.
FAU - Mize, G J
AU  - Mize GJ
FAU - Pineda, M
AU  - Pineda M
FAU - George, D L
AU  - George DL
FAU - Morris, D R
AU  - Morris DR
LA  - eng
GR  - CA39053/CA/NCI NIH HHS/United States
GR  - CA66741/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
SB  - IM
MH  - 5' Untranslated Regions/genetics
MH  - Cells, Cultured
MH  - Choriocarcinoma/pathology
MH  - Female
MH  - Fibroblasts/metabolism
MH  - *Gene Expression Regulation, Neoplastic/drug effects
MH  - HeLa Cells
MH  - Human Growth Hormone/pharmacology
MH  - Humans
MH  - Lung/cytology
MH  - *Nuclear Proteins
MH  - *Oncogenes
MH  - Open Reading Frames
MH  - Promoter Regions, Genetic
MH  - *Protein Biosynthesis
MH  - Proto-Oncogene Proteins/biosynthesis/*genetics
MH  - Proto-Oncogene Proteins c-mdm2
MH  - RNA, Messenger/*genetics
MH  - Ribosomes/metabolism
MH  - Tumor Cells, Cultured/metabolism
MH  - Uterine Neoplasms/pathology
EDAT- 1999/10/19 09:00
MHDA- 2000/10/18 11:01
CRDT- 1999/10/19 09:00
PHST- 1999/10/19 09:00 [pubmed]
PHST- 2000/10/18 11:01 [medline]
PHST- 1999/10/19 09:00 [entrez]
AID - 10.1038/sj.onc.1202949 [doi]
PST - ppublish
SO  - Oncogene. 1999 Oct 7;18(41):5631-7. doi: 10.1038/sj.onc.1202949.