Nuclear localization of long-VEGF is associated with hypoxia and tumor angiogenesis

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that has a pivotal role in normal and pathological angiogenesis. VEGF has a long 5′ untranslated region harboring an open reading frame (ORF) initiated by a CUG codon that is in-frame with the VEGF coding region. The ORF transla...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-06, Vol.332 (1), p.271-278
Main Authors: Rosenbaum-Dekel, Yifat, Fuchs, Alisa, Yakirevich, Evgeny, Azriel, Aviva, Mazareb, Salam, Resnick, Murray B., Levi, Ben-Zion
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Active Transport, Cell Nucleus
AMINO ACIDS
Angiogenesis
ANOXIA
Cell Hypoxia
Cell Line
CELL NUCLEI
Cell Nucleus - metabolism
Cell Nucleus - ultrastructure
CLEAVAGE
GROWTH FACTORS
Humans
Hypoxia
Kidney - blood supply
Kidney - cytology
Kidney - metabolism
L-VEGF
NEOPLASMS
Neoplasms - blood supply
Neoplasms - metabolism
Neoplasms - pathology
Neovascularization, Pathologic - pathology
Neovascularization, Pathologic - physiopathology
Neovascularization, Physiologic - physiology
Nuclear localization
Vascular Endothelial Growth Factor A - metabolism
VEGF
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Summary:Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that has a pivotal role in normal and pathological angiogenesis. VEGF has a long 5′ untranslated region harboring an open reading frame (ORF) initiated by a CUG codon that is in-frame with the VEGF coding region. The ORF translation leads to the expression of a long isoform termed L-VEGF that is extended by an additional 180 amino acids. In this communication, we provide evidence that L-VEGF is subjected to proteolytic cleavage leading to the detachment of the 180 aa extension from the VEGF moiety. Using immunofluorescence staining, we show that upon hypoxia this 180 aa extension translocates to the nuclei of expressing cells. Accordingly, immunohistochemical staining of both normal and tumor tissue samples demonstrated restricted nuclear localization of the ORF, which was correlated with cytoplasmic localization of VEGF. This suggests that the 180 aa ORF is involved in VEGF-mediated angiogenic processes.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.04.123