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Passegué and colleagues discuss recent advances in our understanding of the metabolic control of stem cell function, and how stem cell metabolism relates to homeostasis and ageing.
p53 mutations occur very frequently in human cancer. Besides abrogating the tumour suppressive functions of wild-type p53, many of those mutations also acquire oncogenic gain-of-function activities. Augmentation of proteasome activity is now reported as a common gain-of-function mechanism shared by different p53 mutants, which promotes cancer resistance to proteasome inhibitors.
The Hippo pathway is a key regulator of organ size that has also been implicated in tumorigenesis. Yap, one of the effectors of Hippo signalling, is now reported to support these functions by promoting glutamine synthesis.
De Leo et al. identify a lysosomal response to autophagic cargo during lysosome–autophagosome fusion that involves TLR9 activation and OCRL recruitment, and leads to a regulated local increase in PtdIns(4,5)P2, which is necessary for a normal autophagic flux.
Jiang et al. show that Disabled-2 (Dab2) regulates the switch between autophagy and apoptosis in TGB-β-treated cells, through regulation of the Beclin-1–Vps34 interaction.
Wickström and colleagues describe how mechanical forces applied to epidermal stem cells lead to relocation of emerin to the nuclear envelope and reduced nuclear actin levels, resulting in chromatin changes that influence lineage commitment.
Grintsevich et al. discover that the redox enzyme Mical oxidizes F-actin to promote binding of the F-actin-severing protein cofilin, and that the synergy of Mical and cofilin is necessary and sufficient for F-actin disassembly in Drosophila.
Cox et al. report that Yap induces the expression of glutamine synthetase, thereby elevating glutamine and nitrogen levels for de novo nucleotide synthesis. They show that this promotes hepatomegaly and growth of liver cancer cells in zebrafish.
Walerych et al. show that p53 missense mutants upregulate the proteasome and increase breast cancer cell resistance to proteasome inhibitors. Combined inhibition of p53 mutants and the proteasome leads to increased therapeutic efficacy.
