Share This Author
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing
It is found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated, which may play a key role in mammalian oxygen sensing.
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex.
It is shown that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the Hypoxia-inducible gene REDD1/RTP801 to be inhibited, and that down-regulation of mTOR activity by hyp oxia requires de novo mRNA synthesis and correlates with increased expression of the hypoxIA-Inducible REDD 1 gene.
Role of VHL gene mutation in human cancer.
Preliminary data indicate that HIF plays a critical role in pVHL-defective tumor formation, raising the possibility that drugs directed against HIF or its downstream targets (such as vascular endothelial growth factor) might one day play a role in the treatment of hemangioblastoma and renal cell carcinoma.
Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex
It is shown that the F-box protein Skp2 is polyubiquitinated, and hence earmarked for destruction, by APCCDH1, and accumulation of SCFSKP2 requires prior inactivation of APCC DH1.
The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
It is shown that lenalidomide-bound cereblon acquires the ability to target for proteasomal degradation two specific B cell transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3).
Transformation by the R Enantiomer of 2-Hydroxyglutarate Linked to EglN Activation
Findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.
The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage
The results indicate that c-Abl and p73 are components of a mismatch-repair-dependent apoptosis pathway which contributes to cisplatin-induced cytotoxicity.
Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex.
A novel role for the Cullin-based machinery in regulation of p53 is identified, which is remarkably similar to the von Hippel-Lindau tumor suppressor and SCF E3 ubiquitin ligase complexes.