In this week's PNAS Early Edition, investigators at Johns Hopkins University "describe a synthetic biology strategy for designing protein therapeutics that autonomously activate a therapeutic function in response to a specific cancer marker of choice" and demonstrate its utility "by creating a prodrug-activating enzyme that selectively kills human cancer cells that accumulate the marker hypoxia-inducible factor 1α."
Elsewhere, researchers at the Beatson Institute for Cancer Research in the UK show that "patients who develop prostate tumors with low levels of PTEN and high levels of HER2/3 have a poor prognosis." Further, the Beatson Institute team shows that "targeting Her2 activation to the murine prostate cooperates with Pten loss and drives CaP [prostate cancer] progression."
Investigators at the University of Oxford this week show that iASPP is an evolutionarily conserved inhibitor of p53 and that it is "also a binding partner and negative regulator of p65RelA." The team found that iASPP prevents premature cellular senescence in mouse embryonic fibroblasts, and loss of the p53-inhibitor results in "increased differentiation of primary keratinocytes both in vitro and in vivo," the authors write. Further, the Oxford team presents iASPP as a "key player in controlling epithelial stratification."
In other p53-related news, researchers at University of Medicine and Dentistry of New Jersey and elsewhere show in a paper published online in advance in PNAS this week that a p53 target gene, Parkin, "contributes to the functions of p53 in regulating energy metabolism, especially the Warburg effect, and antioxidant defense, and thus the function of p53 in tumor suppression."