PMID- 9584152
OWN - NLM
STAT- MEDLINE
DCOM- 19980617
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 18
IP  - 6
DP  - 1998 Jun
TI  - Translation of vascular endothelial growth factor mRNA by internal ribosome 
      entry: implications for translation under hypoxia.
PG  - 3112-9
AB  - Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic 
      growth factor that promotes compensatory angiogenesis in circumstances of oxygen 
      shortage. The requirement for translational regulation of VEGF is imposed by the 
      cumbersome structure of the 5' untranslated region (5'UTR), which is incompatible 
      with efficient translation by ribosomal scanning, and by the physiologic 
      requirement for maximal VEGF production under conditions of hypoxia, where 
      overall protein synthesis is compromised. Using bicistronic reporter gene 
      constructs, we show that the 1,014-bp 5'UTR of VEGF contains a functional 
      internal ribosome entry site (IRES). Efficient cap-independent translation is 
      maintained under hypoxia, thereby securing efficient production of VEGF even 
      under unfavorable stress conditions. To identify sequences within the 5'UTR 
      required for maximal IRES activity, deletion mutants were analyzed. Elimination 
      of the majority (851 nucleotides) of internal 5'UTR sequences not only maintained 
      full IRES activity but also generated a significantly more potent IRES. Activity 
      of the 163-bp long "improved" IRES element was abrogated, however, following 
      substitution of a few bases near the 5' terminus as well as substitutions close 
      to the translation start codon. Both the full-length 5'UTR and its truncated 
      version function as translational enhancers in the context of a monocistronic 
      mRNA.
FAU - Stein, I
AU  - Stein I
AD  - Department of Molecular Biology, The Hebrew University-Hadassah Medical School, 
      Jerusalem 91120, Israel.
FAU - Itin, A
AU  - Itin A
FAU - Einat, P
AU  - Einat P
FAU - Skaliter, R
AU  - Skaliter R
FAU - Grossman, Z
AU  - Grossman Z
FAU - Keshet, E
AU  - Keshet E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Lymphokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Endothelial Growth Factors/biosynthesis/*genetics
MH  - Humans
MH  - Lymphokines/biosynthesis/*genetics
MH  - Mice
MH  - Neovascularization, Pathologic/genetics
MH  - Oxygen/*metabolism
MH  - *Protein Biosynthesis
MH  - RNA, Messenger/*metabolism
MH  - Rats
MH  - Ribosomes/*metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
PMC - PMC108893
EDAT- 1998/06/20 00:00
MHDA- 1998/06/20 00:01
PMCR- 1998/06/01
CRDT- 1998/06/20 00:00
PHST- 1998/06/20 00:00 [pubmed]
PHST- 1998/06/20 00:01 [medline]
PHST- 1998/06/20 00:00 [entrez]
PHST- 1998/06/01 00:00 [pmc-release]
AID - 1826 [pii]
AID - 10.1128/MCB.18.6.3112 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1998 Jun;18(6):3112-9. doi: 10.1128/MCB.18.6.3112.