title: Actin cytoskeleton regulates Hippo signaling.
abstract: Hippo pathway controls the organ size by modulating cell proliferation and apoptosis. However, the upstream regulation of hippo signaling by actin cytoskeleton is not clear. To elucidate the role of actin as an upstream regulator of Hippo signaling, the levels of F (filamentous)-actin in cells were elevated using jasplakinolide, an actin-stabilizing drug. Induction of F-actin formation in HeLa cells resulted in decreased phosphorylation of YAP, a key effector molecule for Hippo signaling. The activated YAP is localized to the cell nucleus and YAP increase was associated with increased expression of downstream CCN growth factors CCN1/CYR61 and CCN2/CTGF. The effect of the actin-stabilizing drug was blocked when YAP levels were suppressed in YAP "knock-down" cells. In summary, using an actin-stabilizing drug we show that actin cytoskeleton is one of the upstream regulators of Hippo signaling capable of activating YAP and increasing its downstream CCN growth factors.
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Reddy
authors.forename: Masashi
authors.initials: M
authors.lastname: Deguchi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Aaron J W
authors.initials: AJ
authors.lastname: Hsueh
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism; D047630:Depsipeptides / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D058105:Polymerization / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C501848:CCN1 protein, human; C526317:CCN2 protein, human; D018797:Cell Cycle Proteins; D055515:Cysteine-Rich Protein 61; D047630:Depsipeptides; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; C057531:jasplakinolide; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases
references.citation: Development. 2008 Sep;135(17):2827-38
references.pmid: 18697904
references.citation: Genes Dev. 1995 Mar 1;9(5):534-46
references.pmid: 7698644
references.citation: Cell. 2012 Aug 17;150(4):780-91
references.pmid: 22863277
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1431-6
references.pmid: 20080598
references.citation: Cancer Cell. 2009 Nov 6;16(5):425-38
references.pmid: 19878874
references.citation: J Biol Chem. 1994 May 27;269(21):14869-71
references.pmid: 8195116
references.citation: Chem Biol. 2012 Aug 24;19(8):955-62
references.pmid: 22884261
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Cell. 2003 Aug 22;114(4):457-67
references.pmid: 12941274
references.citation: Curr Opin Cell Biol. 2009 Dec;21(6):837-43
references.pmid: 19846288
references.citation: Acta Otolaryngol. 1986 Mar-Apr;101(3-4):278-85
references.pmid: 2422873
references.citation: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8248-53
references.pmid: 20404163
references.citation: Development. 2011 Jan;138(1):9-22
references.pmid: 21138973
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2569-74
references.pmid: 23359693
references.citation: Development. 2011 Sep;138(18):3907-14
references.pmid: 21831922
references.citation: Science. 2011 Apr 22;332(6028):458-61
references.pmid: 21512031
references.citation: Development. 2011 Jun;138(11):2337-46
references.pmid: 21525075
references.citation: Nature. 2011 Jun 08;474(7350):179-83
references.pmid: 21654799
references.citation: J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10
references.pmid: 17130294
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12405-10
references.pmid: 16894141
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1437-42
references.pmid: 20080689
references.citation: J Cell Biol. 2004 Mar 15;164(6):803-9
references.pmid: 15024029
references.citation: Genes Dev. 2007 Nov 1;21(21):2747-61
references.pmid: 17974916
references.citation: Nat Rev Mol Cell Biol. 2012 Sep;13(9):591-600
references.pmid: 22895435
references.citation: Cell. 2003 Aug 22;114(4):445-56
references.pmid: 12941273
references.citation: Genes Dev. 2008 Jul 15;22(14):1962-71
references.pmid: 18579750
references.citation: Cell. 2005 Aug 12;122(3):421-34
references.pmid: 16096061
references.citation: Am J Respir Cell Mol Biol. 2001 Mar;24(3):282-94
references.pmid: 11245627
references.citation: Genes Dev. 2012 Jan 1;26(1):54-68
references.pmid: 22215811
references.citation: Development. 2008 Dec;135(24):4059-69
references.pmid: 19004856
references.citation: Genes Dev. 2012 Oct 1;26(19):2138-43
references.pmid: 22972936
references.citation: EMBO J. 2011 May 10;30(12):2325-35
references.pmid: 21556047
references.citation: Cell. 2002 Aug 23;110(4):467-78
references.pmid: 12202036
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):E1380-9
references.pmid: 23520048
references.citation: Trends Biochem Sci. 2008 Oct;33(10):461-73
references.pmid: 18789696
references.citation: Cardiovasc Res. 2008 Jan;77(1):64-72
references.pmid: 18006472