PMID- 10228168 OWN - NLM STAT- MEDLINE DCOM- 19990628 LR - 20211203 IS - 0261-4189 (Print) IS - 1460-2075 (Electronic) IS - 0261-4189 (Linking) VI - 18 IP - 9 DP - 1999 May 4 TI - A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator. PG - 2551-62 AB - A protein module called the WW domain recognizes and binds to a short oligopeptide called the PY motif, PPxY, to mediate protein-protein interactions. The PY motif is present in the transcription activation domains of a wide range of transcription factors including c-Jun, AP-2, NF-E2, C/EBPalpha and PEBP2/CBF, suggesting that it plays an important role in transcriptional activation. We show here that mutation of the PY motif in the subregion of the activation domain of the DNA-binding subunit of PEBP2, PEBP2alpha, abolishes its transactivation function. Using yeast two-hybrid screening, we demonstrate that Yes-associated protein (YAP) binds to the PY motif of PEBP2alpha through its WW domain. The C-terminal region of YAP fused to the DNA-binding domain of GAL4 showed transactivation as strong as that of GAL4-VP16. Exogenously expressed YAP conferred transcription-stimulating activity on the PY motif fused to the GAL4 DNA-binding domain as well as to native PEBP2alpha. The osteocalcin promoter was stimulated by exogenous PEBP2alphaA and a dominant negative form of YAP strongly inhibited this activity, suggesting YAP involvement in this promoter activity in vivo. These results indicate that the PY motif is a novel transcription activation domain that functions by recruiting YAP as a strong transcription activator to target genes. FAU - Yagi, R AU - Yagi R AD - Department of Viral Oncology, Institute for Virus Research, Kyoto University, Shogo-in, Sakyo-ku, Kyoto 606-8507, Japan. FAU - Chen, L F AU - Chen LF FAU - Shigesada, K AU - Shigesada K FAU - Murakami, Y AU - Murakami Y FAU - Ito, Y AU - Ito Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Fungal Proteins) RN - 0 (GAL4 protein, S cerevisiae) RN - 0 (Phosphoproteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Transcription Factor AP-2) RN - 0 (Transcription Factors) RN - 0 (YAP-Signaling Proteins) RN - 0 (YAP1 protein, human) RN - 0 (Yap1 protein, mouse) RN - 104982-03-8 (Osteocalcin) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Animals MH - Carrier Proteins/isolation & purification/*metabolism MH - Cell Compartmentation MH - Cell Cycle Proteins MH - Cell Nucleus MH - Cytoplasm MH - DNA-Binding Proteins/genetics/*metabolism MH - Fungal Proteins/genetics/*metabolism MH - Humans MH - Mice MH - Models, Genetic MH - Molecular Sequence Data MH - Mutation MH - Osteocalcin/genetics MH - Phosphoproteins/isolation & purification/*metabolism MH - Promoter Regions, Genetic MH - Protein Binding MH - Recombinant Fusion Proteins/metabolism MH - *Saccharomyces cerevisiae Proteins MH - Transcription Factor AP-2 MH - Transcription Factors/genetics/*metabolism MH - *Transcription, Genetic MH - *Transcriptional Activation MH - YAP-Signaling Proteins PMC - PMC1171336 EDAT- 1999/05/06 00:00 MHDA- 1999/05/06 00:01 PMCR- 2000/05/04 CRDT- 1999/05/06 00:00 PHST- 1999/05/06 00:00 [pubmed] PHST- 1999/05/06 00:01 [medline] PHST- 1999/05/06 00:00 [entrez] PHST- 2000/05/04 00:00 [pmc-release] AID - 10.1093/emboj/18.9.2551 [doi] PST - ppublish SO - EMBO J. 1999 May 4;18(9):2551-62. doi: 10.1093/emboj/18.9.2551.