FKBP25 participates in DNA double-strand break repair

Abstract

FK506-binding proteins (FKBPs) alter the conformation of proteins via cis–trans isomerization of prolyl-peptide bonds. While this activity can be demonstrated in vitro, the intractability of detecting prolyl isomerization events in cells has limited our understanding of the biological processes regulated by FKBPs. Here we report that FKBP25 is an active participant in the repair of DNA double-strand breaks (DSBs). FKBP25 influences DSB repair pathway choice by promoting homologous recombination (HR) and suppressing single-strand annealing (SSA). Consistent with this observation, cells depleted of FKBP25 form fewer Rad51 repair foci in response to etoposide and ionizing radiation, and they are reliant on the SSA repair factor Rad52 for viability. We find that FKBP25’s catalytic activity is required for promoting DNA repair, which is the first description of a biological function for this enzyme activity. Consistent with the importance of the FKBP catalytic site in HR, rapamycin treatment also impairs homologous recombination, and this effect is at least in part independent of mTor. Taken together these results identify FKBP25 as a component of the DNA DSB repair pathway.

FKBP3, a poor prognostic indicator, promotes the progression of LUAD via regulating ferroptosis and immune infiltration

“…It was consistent with the results from Dilworth, who thought that FKBP3 participated in DNA double-strand break repairing. [32] The GSEA analysis also demonstrated that FKBP3 was involved in transcriptional regulation by TP53, which was also proved and confirmed by the reports that FKBP3 induced the degradation of MDM2 and activation of p53 as the novel regulator of the p53 signaling pathway. [33] Moreover, FKBP3 promoted the proliferation of NSCLC cells by interacting with HDAC2, which modulated the acetylation of histone H3K4 and inhibited by p27.…”

Non-translational Connections of eEF1B in the Cytoplasm and Nucleus of Cancer Cells

“…There is not too much data on non-canonical functions of eEF1Bα. This protein interacts with nuclear/cytoplasmic prolylisomerase FKBP25 (FKBP3) (Galat et al, 2014), which is a nucleic acid binding protein involved in both repair of DNA double-strand breaks (Dilworth et al, 2019) and microtubule polymerization (Dilworth et al, 2018). Depletion of nucleoside diphosphate kinase A (NME1) lead to a redistribution of eEF1Bα from the cytoplasm to the endoplasmic reticulum fraction in mouse liver (Bruneel et al, 2011).…”

FKBP25 regulates myoblast viability and migration and is differentially expressed in in vivo models of muscle adaptation

“…From the relatively few studies that have investigated FKBP25's structure and function, it has been found that the PPIase domain is required for protein binding activity and the BTLB domain is needed to facilitate nucleic acid binding [18]. Consistent with this, FKBP25 has been demonstrated to shuttle between the cytoplasm and the nucleus and be involved in nucleic acid binding, DNA repair and interaction with pre‐60S ribosomal subunits [19–22]. Recently, FKBP25 has also been found to bind to microtubules, via its catalytic domain, regulating tubulin polymerisation and mitotic spindle dynamics during the cell cycle [23], suggesting that FKBP25 has the potential to regulate cell proliferation and/or cell migration.…”