| 摘要: | 摘要： The von Hippel–Lindau tumor suppressor gene ( VHL ) has attracted intensive interest not only because its mutations predispose carriers to devastating tumors, but also because it is involved in oxygen sensing under physiological conditions. VHL loss-of-function mutations result in organ-specific tumors, such as hemangioblastoma of the central nervous system and renal cell carcinoma, both untreatable with conventional chemotherapies. The VHL protein is best known as an E3 ubiquitin ligase that targets hypoxia-inducible factor-α (HIF-α), but many diverse, non-canonical cellular functions have also been assigned to VHL , mainly based on studies in cell culture systems. As such, although the HIF-dependent role of VHL is critical, the full spectrum of pathophysiological functions of VHL is still unresolved. Such understanding requires careful cross-referencing with physiologically relevant experimental models. Studies in model systems, such as Caenorhabditis elegans , Drosophila , zebrafish and mouse have provided critical in vivo confirmation of the VHL–HIF pathway, and verification of potentially important cellular functions including microtubule stabilization and epithelial morphogenesis. More recently, animal models have also suggested systemic roles of VHL in hematopoiesis, metabolic homeostasis and inflammation. In this review, the studies performed in model organisms will be summarized and placed in context with existing clinical and in vitro data.
其他題名： Oncogene
出版者： London: Nature Publishing Group UK
出版日期： 2012-05-03
出處： Oncogene, 2012-05, Vol.31 (18), p.2247-2257
資源來源： EBSCOhost Academic Search Premier
版權： Macmillan Publishers Limited 2012
版權： Copyright Nature Publishing Group May 3, 2012
版權： Macmillan Publishers Limited 2012.
版權： 2011 Macmillan Publishers Limited All rights reserved 2011
識別號： ISSN: 0950-9232
識別號： ISSN: 1476-5594
識別號： EISSN: 1476-5594
識別號： DOI: 10.1038/onc.2011.442
識別號： PMID: 21996733
識別號： CODEN: ONCNES |
