In Science Signaling this week, researchers in Utah say that HIF-1α mediates tumor hypoxia to confer a perpetual mesenchymal phenotype for malignant progression. Numerous studies have shown that HIF-1α is over-expressed in many human cancers and up-regulates several hypoxia-responsive genes for cancer growth and survival, the authors write. This study shows that long-term hypoxia drives a perpetual epithelial-mesenchymal transition through up-regulation of the zinc finger E-box binding homeobox protein ZEB2 and that the perpetual epithelial-mesenchymal transition driven by chronic hypoxia depends on HIF-1α induction of genetic alterations rather than its canonical transcriptional activator function, the researchers add.
Also in Science Signaling this week, researchers in the UK and Germany say they've identified a role for SUMO in protein quality control through comparative proteomic analysis. The researchers performed an analysis of SUMO-2 substrates after short- and long-term inhibition of the proteasome with MG132. "Comparisons with changes to the SUMO-2 conjugate subproteome in response to heat stress revealed qualitative and quantitative parallels between both conditions," the authors write. "However, in contrast to heat stress, the MG132-triggered increase in SUMO-2 conjugation depended strictly on protein synthesis, implying that the accumulation of newly synthesized, misfolded proteins destined for degradation by the proteasome triggered the SUMO conjugation response." These findings suggest multiple roles for SUMOs in the cellular response to the accumulation of misfolded proteins, they add.
In Science this week, MIT researchers write that gametogenesis eliminates age-induced cellular damage and resets yeast's life span. Gametes generated by aged cells in eukaryotic organisms show the same replicative potential as gametes generated by young cells, the authors write. "Furthermore, transient induction of a transcription factor essential for later stages of gametogenesis extends the replicative life span of aged cells," they add, which suggests that gamete formation brings about rejuvenation by eliminating age-induced cellular damage.
Also in Science this week, researchers in the US and Canada present a cell cycle phosphoproteome of the yeast centrosome. The team used mass spectrometry to identify 297 phosphorylation sites on centrosomes from different cell cycle stages, and observed "different modes of phosphoregulation via specific protein kinases, phosphorylation site clustering, and conserved phosphorylated residues." Mutating all of the eight cyclin-dependent kinase–directed sites within the core component, Spc42, resulted in lethality and reduced centrosomal assembly, while mutation of one conserved Cdk site within γ-tubulin caused mitotic delay and aberrant anaphase spindle elongation. "Our work establishes the extent and complexity of this prominent posttranslational modification in centrosome biology and provides specific examples of phosphorylation control in centrosome function," the team adds.