• vascular
  • This heterodimer of HIF is a transcription factor that activates genes that encode for proteins such as vascular endothelial growth factor (VEGF) and erythropoietin, proteins that are both involved in angiogenesis. (wikipedia.org)
  • somatic
  • VHL disease is an autosomal-dominant disorder, and tumor development in VHL disease is linked to somatic inactivation of the remaining wild-type VHL allele, leading to loss of the wild-type VHL gene product, VHL protein (pVHL). (rupress.org)
  • pVHL
  • Using green fluorescent protein-tagged end-binding protein 1 to label microtubule plus ends, we found that pVHL does not affect the microtubule growth rate but is needed to orient the growth of microtubules toward the cell periphery, a prerequisite for the formation of cilia. (rupress.org)
  • Moreover, pVHL interacts with the Par3-Par6-atypical PKC (aPKC) polarity complex, suggesting that pVHL may connect Par3-Par6-aPKC polarity proteins to microtubule capture and ciliogenesis. (rupress.org)
  • We showed that the P86L substitution stimulated small aggregate formation, the P146A mutation increased large inclusion formation while I151S destabilized pVHL. (biologists.org)
  • Hydroxylation of HIF creates a binding site for pVHL (the protein transcript of the VHL gene). (wikipedia.org)
  • pVHL directs the polyubiquitylation of HIF1A, ensuring that this protein will be degraded by the proteasome. (wikipedia.org)
  • gene
  • The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. (wikipedia.org)
  • time
  • The left panel shows the evolutionary history of each tumor, the middle panel represents a snapshot of the tumor at a given time, and the right panel shows the potential future development. (biomedcentral.com)
  • several
  • Pathologists have long recognized heterogeneity within tumors at the morphological level, and heterogeneity at the genetic level was first shown several decades ago by cytogenetic analyses (as reviewed by Navin and Hicks [ 5 ]), but more recent sequencing studies have provided deeper insights into the full extent of intertumor and intratumor heterogeneity. (biomedcentral.com)
  • study
  • We also describe how subclonal diversity might contribute to the limitations of targeted therapies and how it can be leveraged to study the evolutionary history of a tumor and to optimize clinical trial design. (biomedcentral.com)