Btbd2-KO Mouse

Btbd2, along with its paralog BTBD1, belongs to a small family of uncharacterized animal-specific proteins. These proteins contain a BTB-domain and are Kelch-like. BTBD2 is involved in interacting with Topoisomerase I (TOP1), and they co-localize in cytoplasmic bodies [1]. BTBD2 may also be related to the double-strand break repair pathway as its polymorphisms are associated with glioblastoma survival [2].

In research, it was found that the interaction between BTBD2 and TOP1 requires specific human TOP1 residues. RNAi of BTBD2 in old world monkey and human cells increases permissiveness to HIV-1 infection, suggesting its possible role in HIV-1 restriction [3]. Also, the E3-RING Cullin 3 ligase, in complex with BTBD2, promotes TOP1-cleavage complex ubiquitination and subsequent proteasomal degradation, which is part of the adaptive response to TOP1 inhibitors [4]. Moreover, BTBD2 enables the interaction and activation of TOP1 during mitosis in the context of HNF1β bookmarking, playing a role in chromatin remodeling and gene reactivation after mitotic exit [5].

In conclusion, BTBD2 is significantly involved in multiple biological processes, mainly through its interaction with TOP1. Its role in processes like HIV-1 restriction, the response to TOP1 inhibitors, and chromatin remodeling provides insights into these complex biological mechanisms. The association of its polymorphisms with glioblastoma survival also highlights its importance in understanding this disease [2,3,4,5].