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Systemic VHL gene functions and the VHL disease
Author(s) -
Bader Hannah L.,
Hsu Tien
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.04.032
Subject(s) - disease , gene , cancer research , genetics , medicine , biology , bioinformatics
The von Hippel‐Lindau tumor suppressor gene ( VHL ) is best known as an E3 ubiquitin ligase that negatively regulates the hypoxia inducible factor (HIF). VHL mutations are the genetic defects underlying several human diseases including polycythemia, familial VHL tumor syndrome and sporadic renal cell carcinoma. VHL mutations can lead to cell‐autonomous phenotypes in the tumor cells. However, non‐tumor cell‐autonomous functions of VHL have also been noted. VHL tumor‐derived cytokines can promote inflammation and induce mobilization of endothelial progenitor cells. Up‐regulation of HIF caused by VHL loss‐of‐function mutants, including heterozygotes, has been shown to increase the activities of hematopoietic stem cells, endothelial cells and myeloid cells. As such, systemic functions of VHL likely play important roles in the development of VHL disease.