The subcellular relocalization of FKBP51 relates to its phosphorylation status

ZGAJNAR NR, DANERI-BECERRA C, GALIGNIANA MD

Congreso; The subcellular relocalization of FKBP51 relates to its phosphorylation status; 2022

The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein kinases, protein phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favour the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. We postulated that one of the most simple and flexible strategies for regulating pathways and subcellular localization could be phosphorylation. In this study it is demonstrated that the various bands of FKBP51 revealed after a resolutive electrophoresis are phosphorylated isoforms of the immunophilin, as demonstrated by its disappearance after the action of alkaline phosphatase. FKBP51 translocates from mitochondria to the nucleus upon the onset of various stress stimuli such as oxidative stress, a phenomenon that favours the dephosphorylation of tyrosine residues of FKBP51. Structural studies predict the existence of several phosphorylation sites, one of them a key tyrosine located at the C-terminal tail of the immunophilin. Interestingly, oxidative stress favours its dephosphorylation and proteasome degradation of FKBP51, whereas the presence of the immunophilin ligand FK506 protects the persistence of this post-translational modification and consequently the stability of the protein under oxidative conditions.