Strano S, Munarriz E, Rossi M, Castagnoli L, Shaul Y, Sacchi A, Oren M, Sudol M, Cesareni G, Blandino G
Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Rome 00158, Italy.
J Biol Chem. 2001 May 4;276(18):15164-73. doi: 10.1074/jbc.M010484200. Epub 2001 Jan 24.
Specific protein-protein interactions are involved in a large number of cellular processes and are mainly mediated by structurally and functionally defined domains. Here we report that the nuclear phosphoprotein p73 can engage in a physical association with the Yes-associated protein (YAP). This association occurs under physiological conditions as shown by reciprocal co-immunoprecipitation of complexes from lysates of P19 cells. The WW domain of YAP and the PPPPY motif of p73 are directly involved in the association. Furthermore, as required for ligands to group I WW domains, the terminal tyrosine (Y) of the PPPPY motif of p73 was shown to be essential for the association with YAP. Unlike p73alpha, p73beta, and p63alpha, which bind to YAP, the endogenous as well as exogenously expressed wild-type p53 (wt-p53) and the p73gamma isoform do not interact with YAP. Indeed, we documented that YAP interacts only with those members of the p53 family that have a well conserved PPXY motif, a target sequence for WW domains. Overexpression of YAP causes an increase of p73alpha transcriptional activity. Differential interaction of YAP with members of the p53 family may provide a molecular explanation for their functional divergence in signaling.
特定的蛋白质-蛋白质相互作用参与了大量的细胞过程，并且主要由结构和功能明确的结构域介导。在此我们报告，核磷蛋白p73可与Yes相关蛋白（YAP）发生物理结合。如通过对P19细胞裂解物中的复合物进行相互免疫共沉淀所显示，这种结合在生理条件下发生。YAP的WW结构域和p73的PPPPY基序直接参与了这种结合。此外，正如I类WW结构域配体所要求的，p73的PPPPY基序的末端酪氨酸（Y）对于与YAP的结合至关重要。与能结合YAP的p73α、p73β和p63α不同，内源性以及外源性表达的野生型p53（wt-p53）和p73γ亚型不与YAP相互作用。实际上，我们证明YAP仅与p53家族中具有保守PPXY基序（WW结构域的靶序列）的那些成员相互作用。YAP的过表达导致p73α转录活性增加。YAP与p53家族成员的差异相互作用可能为它们在信号传导中的功能差异提供分子解释。
