title: Lats2 modulates adipocyte proliferation and differentiation via hippo signaling.
abstract: First identified in Drosophila and highly conserved in mammals, the Hippo pathway controls organ size. Lats2 is one of the core kinases of the Hippo pathway and plays major roles in cell proliferation by interacting with the downstream transcriptional cofactors YAP and TAZ. Although the function of the Hippo pathway and Lats2 is relatively well understood in several tissues and organs, less is known about the function of Lats2 and Hippo signaling in adipose development. Here, we show that Lats2 is an important modulator of adipocyte proliferation and differentiation via Hippo signaling. Upon activation, Lats2 phosphorylates YAP and TAZ, leading to their retention in the cytoplasm, preventing them from activating the transcription factor TEAD in the nucleus. Because TAZ remains in the cytoplasm, PPARγ regains its transcriptional activity. Furthermore, cytoplasmic TAZ acts as an inhibitor of Wnt signaling by suppressing DVL2, thereby preventing β-catenin from entering the nucleus to stimulate TCF/LEF transcriptional activity. The above effects contribute to the phenotype of repressed proliferation and accelerated differentiation in adipocytes. Thus, Lats2 regulates the balance between proliferation and differentiation during adipose development. Interestingly, our study provides evidence that Lats2 not only negatively modulates cell proliferation but also positively regulates cell differentiation.
authors: State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
authors: Yang
authors: Y
authors: An
authors: Qianqian
authors: Q
authors: Kang
authors: Yaofeng
authors: Y
authors: Zhao
authors: Xiaoxiang
authors: X
authors: Hu
authors: Ning
authors: N
authors: Li
mesh_terms: D041721:3T3-L1 Cells; D000217:Acyltransferases; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D060449:Wnt Signaling Pathway; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D000217:Acyltransferases; C486363:tafazzin protein, mouse; C522633:LATS2 protein, mouse; D017346:Protein Serine-Threonine Kinases
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