title: IQGAP1 Binds to Yes-associated Protein (YAP) and Modulates Its Transcriptional Activity.
abstract: During development, the Hippo signaling pathway regulates key physiological processes, such as control of organ size, regeneration, and stem cell biology. Yes-associated protein (YAP) is a major transcriptional co-activator of the Hippo pathway. The scaffold protein IQGAP1 interacts with more than 100 binding partners to integrate diverse signaling pathways. In this study, we report that IQGAP1 binds to YAP and modulates its activity. IQGAP1 and YAP co-immunoprecipitated from cells. In vitro analysis with pure proteins demonstrated a direct interaction between IQGAP1 and YAP. Analysis with multiple fragments of each protein showed that the interaction occurs via the IQ domain of IQGAP1 and the TEAD-binding domain of YAP. The interaction between IQGAP1 and YAP has functional effects. Knock-out of endogenous IQGAP1 significantly increased the formation of nuclear YAP-TEAD complexes. Transcription assays were performed with IQGAP1-null mouse embryonic fibroblasts and HEK293 cells with IQGAP1 knockdown by CRISPR/Cas9. Quantification demonstrated that YAP-TEAD-mediated transcription in cells lacking IQGAP1 was significantly greater than in control cells. These data reveal that IQGAP1 binds to YAP and modulates its co-transcriptional function, suggesting that IQGAP1 participates in Hippo signaling.
authors.affiliation: From the Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Samar
authors.initials: S
authors.lastname: Sayedyahossein
authors.affiliation: From the Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Li
authors.affiliation: From the Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hedman
authors.affiliation: From the Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Chase J
authors.initials: CJ
authors.lastname: Morgan
authors.affiliation: From the Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland 20892 david.sacks2@nih.gov.
authors.forename: David B
authors.identifier: 0000-0003-3100-0735
authors.initials: DB
authors.lastname: Sacks
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D000091102:YAP-Signaling Proteins; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C101203:IQ motif containing GTPase activating protein 1; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse; D020703:ras GTPase-Activating Proteins; D017346:Protein Serine-Threonine Kinases
keywords: Hippo pathway; IQGAP1; cell signaling; protein complex; transcription factor; yes-associated protein (YAP)