P53凋亡刺激蛋白2
编号:XY- 1283R
This gene encodes a member of the ASPP(apoptosis-stimulating protein of p53 2) family of p53 interacting proteins. The protein contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. It is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family. Multiple transcript variants encoding different isoforms have been found for this gene. 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. [SUBCELLULAR LOCATION] Cytoplasm, perinuclear region. Nucleus.
Function : Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions. Regulates TP53 by enhancing the DNA binding and transactivation function of 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. Its apoptosis-stimulating activity is inhibited by its interaction with DDX42.
Subunit : Binds to the central domain of 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 TP53. Interacts with APC2 and APPBP1. Interacts with DDX42 (via the C-terminus); the interaction is not inhibited by TP53BP2 ubiquitination and is independent of p53/TP53.
Subcellular Location : Cytoplasm, perinuclear region. Nucleus. Note=Predominantly found in the perinuclear region. Some small fraction is nuclear. Sequester in the cytoplasm on overexpression of DDX42.
Tissue Specificity : Widely expressed. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocyte. Reduced expression in breast carcinomas expressing a wild-type TP53 protein. Overexpressed in lung cancer cell lines.
Similarity : Belongs to the ASPP family.
Contains 2 ANK repeats.
Contains 1 SH3 domain.
Database links : UniProtKB/Swiss-Prot: Q13625.2
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.