Bindarit receptor YAP TAZ nuclear function is also influence

YAP/TAZ nuclear function is also influenced by interaction with the TEAD family of transcription factors [96, 97, 98, 99, 100, 101]. The RAC1 Bindarit receptor exchange factor protein TIAM1 has recently been linked to YAP/TAZ regulation in the nucleus and cytoplasm. Nuclear TIAM1 inhibits YAP/TAZ binding to TEAD4, while cytoplasmic TIAM1 promotes YAP/TAZ degradation via the β-catenin destruction complex []. TEAD nuclear localisation is antagonised by p38 MAPK, suggesting that YAP activity can be overridden by cellular stress even in the absence of core kinase activity []. Therefore, YAP nuclear function requires not only low LATS-mediated phosphorylation but also the presence of nuclear TEAD []. Finally, the RNA-binding protein MASK and the nuclear speckle-localised kinase Homeodomain-interacting protein kinase (Hipk) have been suggested to aid Yki/YAP function in the nucleus, though the mechanistic details are not yet elucidated [104, 105, 106, 107]. Thus, the control of Yki/YAP nucleo-cytoplasmic shuttling dynamics, as well as the modulation of their activity in the nucleus remain little explored areas in need of investigation.
Conclusion
Conflict of interest
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as:
Acknowledgements We apologise to those whose work we omitted due to space limitations. AF was supported by a Cancer Research UK PhD fellowship. Research in NT's laboratory is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001175), the UK Medical Research Council (FC001175) and the Wellcome Trust (FC001175), as well as a Wellcome Trust Investigator award (107885/Z/15/Z). PSR was a recipient of funds from Cancer Research UK and The Academy of Medical Sciences/Wellcome Trust Springboard Award.
Introduction Signaling pathways that contain a Sterile 20-like kinase that activates a nuclear Dbf2-related (NDR) family kinase exist throughout eukaryotes, regulate different biological processes, and are sometimes referred to as Hippo-like signaling modules (Hergovich and Hemmings, 2012). Antecedent examples of this type of kinase module include the Saccharomyces cerevisiae mitotic exit network and the Schizosaccharomyces pombe septation initiation network, which control cell division and cytokinesis (Bardin and Amon, 2001). The best-defined signaling module of this kind in metazoans forms the core of the Hippo pathway, which operates in insects and mammals to control processes such as organ size and cell fate (Pan, 2010, Halder and Johnson, 2011, Harvey et al., 2013). In addition, a related pathway has been identified in mammals and consists of the Sterile 20-like kinase Mammalian Sterile Twenty-like 3 (MST3) (and possibly its close homologs MST4 and STK25), which can regulate the NDR family kinases NDR1 and NDR2 (aka STK38 and STK38L) (Hergovich, 2013). In some instances, Sterile 20-like kinases have been reported to regulate more than one type of NDR family kinase. For example, Hippo (Hpo) can regulate both Tricornered (Trc) and Warts (Wts) in Drosophila melanogaster peripheral nervous system dendrites (Emoto et al., 2006). In addition, in mammals, the Hpo orthologs MST1 and MST2 can regulate both the Trc orthologs NDR1 and NDR2 and the Wts orthologs LATS1 and LATS2 (Yu and Guan, 2013, Hergovich and Hemmings, 2009, Avruch et al., 2012). The sole D. melanogaster ortholog of NDR1/2, Trc, controls hair and bristle development in the wing, thorax, and antennae, as well as dendrite tiling and branching in the peripheral nervous system (Geng et al., 2000, Emoto et al., 2006). In D. melanogaster, the sole ortholog of MST3/MST4/STK25, Germinal center kinase III (GckIII), regulates tracheal development together with the non-catalytic protein Cerebral cavernous malformation 3 (CCM3). Loss of GckIII results in a characteristic dilation at the transition zone of the terminal cell, associated with abnormal localization and abundance of septate junction proteins and the apical membrane protein Crumbs (Song et al., 2013). The mechanism by which GckIII is regulated in trachea is unknown, and it is also unclear whether GckIII controls tracheal development by regulating an NDR family kinase.