Wrap53-flox Mouse

Wrap53, also known as WD repeat containing antisense to TP53, encodes an antisense transcript for tumor protein p53 (TP53) stabilization (WRAP53α) and a functional protein (WRAP53β, WDR79, or TCAB1). The WRAP53β protein acts as a scaffolding protein crucial for telomerase localization, telomere assembly, Cajal body integrity, and DNA double-strand break repair. It contains WD40 domains mediating various cell interactions [1].

In an in vivo mouse model of stroke, oxygen/glucose-deprived (OGD) neurons showed that DNA double-strand breaks (DSBs) correlated with WRAP53 up-regulation, which translocated to the nucleus to activate DSB repair response. Neurons expressing the Wrap53 human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G) had faster nuclear translocation of WRAP53, and patients with this SNP had less infarct volume and better functional outcome after stroke, indicating WRAP53 promotes DNA repair, neuronal survival, and functional recovery after stroke [2]. In non-small cell lung cancer cells, knockdown of WRAP53-1α and WRAP53-1β had different effects on cell behaviors depending on p53 expression [3]. Low levels of WRAP53 protein predict local recurrence and breast cancer-related death, and low WRAP53 RNA levels may indicate radioresistance [4].

In conclusion, Wrap53 is essential for multiple cellular processes such as telomere-related functions and DNA repair. Studies using in vivo models like the stroke mouse model have revealed its significance in stroke recovery, and its role in cancer-related processes like non-small cell lung cancer cell behaviors and breast cancer prognosis and radioresistance. These findings contribute to understanding the biological functions of Wrap53 in disease conditions, providing potential directions for disease treatment and prevention.