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The class III phosphoinositide 3-kinase VPS34 regulates autophagosome formation. Three groups have developed VPS34 inhibitors and shown their utility in investigating and defining autophagic processes.
The microcephaly protein, Cep215, contributes to the engagement of duplicated centrioles in interphase. Now two distinct pools of Cep215 at centrosomes are identified, one bound to Cep68 and the other to pericentrin. Plk1-mediated degradation of Cep68 and separase-mediated cleavage of pericentrin release both pools of Cep215, thereby promoting centriole disengagement.
Hippo signalling has been associated with many important tissue functions including the regulation of organ size. In the intestinal epithelium differing functions have been proposed for the effectors of Hippo signalling, YAP and TAZ1. These are now shown to have a dual role in the intestinal epithelium, regulating both stem cell proliferation and differentiation along a specific secretory lineage.
Imajo and colleagues report that the Hippo signalling pathway components YAP and TAZ act via TEAD to promote intestinal stem/progenitor cell proliferation and via Klf4 to trigger their differentiation.
mTOR signalling both inhibits autophagy and promotes cell proliferation. Cecconi and colleagues report that AMBRA1 links these two processes by facilitating dephosphorylation and degradation of the proto-oncogene c-Myc.
Pagano and colleagues find that Plk1 and the E3 ubiquitin ligase SCFβTrCP mediate degradation of the centrosome cohesion protein Cep68 and show this mediates removal of Cep215 from the PCM and subsequent centriole separation in late mitosis.
Rosen and colleagues perform epigenomic and transcriptomic analyses of insulin-resistant cells, and report that the vitamin D receptor and glucocorticoid receptor mediate transcriptional responses that promote insulin resistance.
Moisan, Cowan and colleagues perform a small-molecule screen to identify compounds that promote white-to-brown adipocyte conversion in vitro. They report that two inhibitors of the JAK–STAT signalling pathway stimulate browning of human adipocytes.
Sahai and colleagues delineate a pathway through which components of the STRIPAK complex promote amoeboid cancer cell migration by regulating the linkage of the actomyosin network to the plasma membrane.
Giancotti and colleagues report that the Rnd1 Rho GTPase suppresses the epithelial–mesenchymal transition and mammary tumorigenesis by inhibiting Ras-MAPK signalling through a Plexin B1–Rap1–p120 Ras-GAP signalling axis.
Wu and colleagues report that under hypoxic conditions the LATS2 kinase is targeted for degradation by the SIAH2 ubiquitin ligase, leading to inhibition of the Hippo kinase cascade and activation of YAP, which promotes tumour growth.
