Expression Level and Intracellular Localization of pVHL Modulate the HIF System

Does the Expression Level and Intracellular Localization of pVHL Modulate the HIF System  

An important question is whether alterations in the amoimt and/or eellular localization of pVHL could also regulate the HIF system. pVHL is predominantly found in the cytoplasmic and membrane compartments (36,65-67). Since the role of HIF alpha chains is in the nucleus there is an apparent paradox. However, pVHL continuously moves through the nuclear compartment, from which it is actively transported (68,69). This continuous flux through the nuclear compartment may accoxmt for apparently differing reports concerning intracellular localization of pVHL (65,70). Clearly shuttling of pVHL through the nuclear compartment provides a potential mechanism by which hydroxylated HIF alpha chains in the nucleus can be captured and ubiquitylated. 

What Other Processes Are Mediated by pVHL and Do These Involve Prolyl Hydroxylatlon  

VHL s role in recognizing the oxygen-dependent destruction domain of HIF alpha after conversion to the hydroxyproUne-containing form appears not to be the only role of this tumor suppressor protein. pVHL s involvement in other processes can be considered in three categories regulation of aspects of HIF other than ODDD- 

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