TP53BP2
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Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. Multiple transcript variants encoding different isoforms have been found for this gene.
Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. Multiple transcript variants encoding different isoforms have been found for this gene.
Function
ASPP2 plays a central role in regulation of apoptosis and cell growth via its interactions. ASPP2 regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. ASPP2 binds to wild-type p53 but fails to bind to mutant p53, suggesting that ASPP2 may be involved in the ability of wild-type p53 to suppress transformation. ASPP2 induces apoptosis but no cell cycle arrest.
Structure
ASPP2 contains several structural and functional domains. Its N-terminus (residues 1–83) has the structure of a β-grasp ubiquitin-like fold. It is followed by a predicted α-helical domain located between aa 123 and 323. and a proline-rich (ASPP2 Pro) domain between aa 674 and 902. The C-terminal part of ASPP2 contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP2 is found in the perinuclear region of the cytoplasm.
Family members
The ASPP family includes ASPP1, ASPP2, and iASPP. The name ASPP stands for apoptosis stimulating protein of p53, the name emphasizes the ankyrin repeats, SH3 domain, and proline-rich domains that characterize this family. The three family members come from different genes but ASPP1 and ASPP2 share a greater sequence similarity than either does with iASPP as the N terminus of iASPP has no homology with ASPP1 and ASPP2. The sequence similarities among ASPP family members indicates that ASPP1 and ASPP2 probably have similar biological functions that differ from that of iASPP. The family plays a key role in apoptosis regulation in the intrinsic and extrinsic apoptotic pathways. ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis.
Binding partners
ASPP2 is the ASPP family member with the most known binding partners. The highly conserved C-terminus was first known to bind to p53 through its ankyrin repeats and SH3 domain in 1994 by a yeast two hybrid system and it was called p53 Binding Protein 2 (53BP2). Other binding partners have been discovered through the years, indicating the importance of the ankyrin repeats and SH3 domains for protein-protein interactions. Some of the known binding partners of ASPP2 include BCL2, p63, p73, Hepatitis C virus core protein, Amyloid-b-Precursor Protein-Binding Protein 1 (APP-BP1), YES-Associated Protein (YAP), Adenomatosis Polyposis Coli 2 (APC2), RelA/p65, Protein Phosphatase 1 (PP1) and NFκB (p65)
Expression
The expression of ASPP2 is encoded by the gene TP53BP2 and is located in the long arm of chromosome 1 at q42.1. Northern-blot analyses showed that the ASPP2/53BP2 mRNA was expressed in many human tissues such as heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, but at varying levels. The highest expression level of ASPP2 was detected in skeletal tissue.
References
Further reading
Text derived from https://en.wikipedia.org/w/index.php?oldid=1300852095 under CC BY-SA 4.0; modifications have been made.