| First Author | Yagi R | Year | 1999 |
| Journal | EMBO J | Volume | 18 |
| Issue | 9 | Pages | 2551-62 |
| PubMed ID | 10228168 | Mgi Jnum | J:54971 |
| Mgi Id | MGI:1336834 | Doi | 10.1093/emboj/18.9.2551 |
| Citation | Yagi R, et al. (1999) A WW domain-containing yes-associated protein (YAP) is a novel transcriptional co-activator. EMBO J 18(9):2551-62 |
| abstractText | 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. |
