Serbp1-flox Mouse

Serbp1, also known as SERPINE1 mRNA binding protein 1, is an RNA binding protein that lacks canonical RNA-binding domains and is mostly disordered [2,5]. It plays crucial roles in multiple biological processes. SERBP1 is involved in pathways such as stress granule clearance, splicing, cell division, ribosome biogenesis, apoptosis regulation, and ferroptosis regulation [1-4]. It is also associated with the DNA damage response, mRNA metabolism, and translation regulation, making it biologically important in normal cell function and disease-related processes [7,8,9].

In vivo, depletion of SERBP1 in testicular cells leads to increased germ cell apoptosis upon scrotal heat stress, suggesting its role in protecting male germ cells from thermostimuli damage. It does this by regulating 26S proteasome activity and G3BP1 ubiquitination to facilitate stress granule clearance [1]. In HeLa cells, overexpression of SERBP1 induces apoptosis, with downregulated genes enriched in cell proliferation and apoptosis pathways, and genes with SERBP1-regulated alternative splicing enriched in transcriptional regulation and metabolic processes related to tumorigenesis [3]. KSHV-encoded vIL-6 promotes SIRT3-induced deacetylation of SERBP1, which inhibits ferroptosis and enhances cellular transformation [4]. In neurons, silencing of SERBP1 relieves KCC2 repression by miR-92 [6]. SERBP1 also affects homologous recombination-mediated DNA repair by regulating CtIP translation during S phase [8].

In conclusion, SERBP1 is a multifunctional protein involved in stress granule clearance, cell apoptosis, ferroptosis regulation, and DNA repair. Its role in protecting male germ cells from heat-induced apoptosis, as well as its involvement in tumor-related processes like apoptosis and metabolic regulation in HeLa cells, and KSHV-induced cellular transformation, highlight its importance in disease-related research. The study of SERBP1 using in vivo models helps in understanding its complex functions and provides potential targets for disease treatment.