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SUMOylation activates large tumour suppressor 1 to maintain the tissue homeostasis during Hippo signalling
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SUMOylation activates large tumour suppressor 1 to maintain the tissue homeostasis during Hippo signalling
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Journal Article
SUMOylation activates large tumour suppressor 1 to maintain the tissue homeostasis during Hippo signalling
2021
Overview
Large tumour suppressor (LATS) 1/2, the core kinases of Hippo signalling, are critical for maintaining tissue homeostasis. Here, we investigate the role of SUMOylation in the regulation of LATS activation. High cell density induces the expression of components of the SUMOylation machinery and enhances the SUMOylation and activation of Lats1 but not Lats2, whereas genetic deletion of the SUMOylation E2 ligase,
Ubc9
, abolishes this Lats1 activation. Moreover, SUMOylation occurs at the K830 (mouse K829) residue to activate LATS1 and depends on the PIAS1/2 E3 ligase. Whereas the K830 deSUMOylation mutation of LATS1 found in the human metastatic prostate cancers eliminates the kinase activity by attenuating the formation of the phospho-MOB1/phospho-LATS1 complex. As a result, the LATS1(K830R) transgene phenocopies
Yap
transgene to cause the oversized livers in mice, whereas Lats1(K829R) knock-in phenocopies the deletion of
Lats1
in causing the reproductive and endocrine defects and ovary tumours in mice. Thus, SUMOylation-mediated LATS1 activation is an integral component of Hippo signalling in the regulation of tissues homeostasis.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 96/95
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Cancer
/ Cellular signal transduction
/ Female
/ Humans
/ Kinases
/ Male
/ Medicine
/ Mice
/ Oncology
/ Post-translational modification
/ Protein Serine-Threonine Kinases - genetics
/ Protein Serine-Threonine Kinases - metabolism
/ Tissues
/ Tumor Suppressor Proteins - genetics
/ Tumor Suppressor Proteins - metabolism
/ Tumors
/ Ubiquitin-Conjugating Enzymes - genetics
/ Ubiquitin-Conjugating Enzymes - metabolism
/ YAP-Signaling Proteins - genetics
