p53凋亡刺激蛋白(apoptosis stimulating protein of p53,ASPP)家族是近年来发现的一个新蛋白家族,它包括3个成员:ASPP1、ASPP2和
iASPP。其中ASPP1和ASPP2能够与p53蛋白结合增强该蛋白的促进细胞凋亡的功能,发挥抑制肿瘤的作用;而iASPP与ASPP1和ASPP2的功能截然相反,它能够和ASPP1或ASPP2竞争性地与p53结合,抑制ASPP1或ASPP2的促进凋亡作用,具有癌基因的功能。三者的结构相似,但功能却完全不同,通过研究三者的关系、促进肿瘤细胞内ASPP1或ASPP2的高表达以及抑制iASPP的表达有可能促进肿瘤细胞的凋亡,成为肿瘤治疗的新靶点.
[FUNCTION] Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions. Regulates p53/TP53 by enhancing the DNA binding and transactivation function of p53/TP53 on the promoters of proapoptotic genes in vivo. Inhibits the ability of APPBP1 to conjugate NEDD8 to CUL1, and thereby decreases APPBP1 ability to induce apoptosis. Impedes cell cycle progression at G2/M (By similarity).
[SUBUNIT] Binds to the central domain of p53/TP53 as well as to BCL2. Interacts with protein phosphatase 1. Interacts with RELA NF-kappa-B subunit. This interaction probably prevents the activation of apoptosis, possibly by preventing its interaction with p53/TP53. Interacts with APC2 and APPBP1 (By similarity).
[INTERACTION] P35569:Irs1; NbExp=1; IntAct=EBI-645416, EBI-400825.
[SUBCELLULAR LOCATION] Cytoplasm, perinuclear region (By similarity). Nucleus (By similarity). Note=Predominantly found in the perinuclear region (By similarity). Some small fraction is nuclear (By similarity).
[DOMAIN] The ankyrin repeats and the SH3 domain are required for specific interactions with p53/TP53 (By similarity). a
[SIMILARITY] Belongs to the ASPP family.
[SIMILARITY] Contains 2 ANK repeats.
[SIMILARITY] Contains 1 SH3 domain