Apoptosis-stimulating protein of p53 2 kappa isoform mRNA (ASPP2κ mRNA)

ASPP2κ mRNA is a stress-inducible, oncogenic splice variant of the TP53BP2 gene, which encodes the tumor suppressor Apoptosis-stimulating protein of p53 2 (ASPP2) [1, 2]. This specific isoform is generated through the skipping of exon 17, leading to a premature stop codon and a truncated protein that lacks the critical C-terminal p53-binding domains [2, 3]. Consequently, the ASPP2κ protein acts in a dominant-negative fashion, sequestering or otherwise interfering with the pro-apoptotic functions of wild-type ASPP2 and p53 [1, 4]. This molecular shift impairs the cell's ability to undergo programmed cell death in response to DNA damage, thereby promoting tumor cell survival, proliferation, and resistance to chemotherapy [1, 5]. ASPP2κ is frequently overexpressed in hematologic malignancies like acute myeloid leukemia and solid tumors such as glioblastoma and rhabdomyosarcoma [4, 5]. Experimental strategies such as antisense oligonucleotides (ASOs) and siRNAs are being developed to specifically silence this isoform and restore the apoptotic checkpoint, making it a promising target for precision oncology [3, 5].

Other names

TP53BP2 kappa mRNAASPP2 kappa transcriptOncogenic ASPP2 splice variant

mRNA silencing via antisense oligonucleotides or RNA interference to restore wild-type ASPP2 function