Post-translational modifications and stress adaptation: the paradigm of FKBP51

Rein, Theo

doi:10.1042/bst20190332

Cited by 10 publications

(5 citation statements)

References 91 publications

(135 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Parkin and FKBP51 interaction may play a prominent role in the regulation of microtubule-related proteins, such as MAP2, Tubulin, and Tau. It is probable that FKBP51 performs these functions via its isomerase activity and its involvement in the phosphorylation, ubiquitination, and lipidation of other proteins (Rein, 2020a;Rein, 2020b). We propose a model for their interaction based on our ndings (Figure 7).…”

Section: Discussionmentioning

confidence: 81%

FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin

Qiu

Zhong

Righter

et al. 2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

FK506-binding protein 51 (encoded by Fkpb51) has been associated with stress-related mental illness. To identify its function, we studied the morphological consequences of Fkbp51 deletion. Arti cial Intelligence-assist morphological analysis identi ed that Fkbp51 knock-out (KO) mice possess more elongated CA and DG but shorter in height in coronal section when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls, pharmacological manipulation experiments suggest that this may occur through regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support that FKBP51 regulates microtubule-associated protein expression. Furthermore, in the absence of differences in mRNA expression, Fkbp51 KO hippocampus exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory of Parkin by FKBP51 and signi cance of their interaction on disease onset.

show abstract

Section: Discussionmentioning

confidence: 81%

FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin

Qiu

Zhong

Righter

et al. 2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…FKBP51 was first identified as a GR binding protein, negatively regulating GR activity, but further studies revealed its role in post-translational protein modification (PTM) [ 5 , 58 ]. Consistently, Fkpb51 elimination enhances GR inhibition and lowers glucocorticoid expression in serum.…”

Section: Discussionmentioning

confidence: 99%

Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity

Qiu,

Zhong,

Dou

et al. 2024

Cell Biosci

View full text Add to dashboard Cite

Background and aims Previously, we found that FK506 binding protein 51 (Fkbp51) knockout (KO) mice resist high fat diet-induced fatty liver and alcohol-induced liver injury. The aim of this research is to identify the mechanism of Fkbp51 in liver injury. Methods Carbon tetrachloride (CCl4)-induced liver injury was compared between Fkbp51 KO and wild type (WT) mice. Step-wise and in-depth analyses were applied, including liver histology, biochemistry, RNA-Seq, mitochondrial respiration, electron microscopy, and molecular assessments. The selective FKBP51 inhibitor (SAFit2) was tested as a potential treatment to ameliorate liver injury. Results Fkbp51 knockout mice exhibited protection against liver injury, as evidenced by liver histology, reduced fibrosis-associated markers and lower serum liver enzyme levels. RNA-seq identified differentially expressed genes and involved pathways, such as fibrogenesis, inflammation, mitochondria, and oxidative metabolism pathways and predicted the interaction of FKBP51, Parkin, and HSP90. Cellular studies supported co-localization of Parkin and FKBP51 in the mitochondrial network, and Parkin was shown to be expressed higher in the liver of KO mice at baseline and after liver injury relative to WT. Further functional analysis identified that KO mice exhibited increased ATP production and enhanced mitochondrial respiration. KO mice have increased mitochondrial size, increased autophagy/mitophagy and mitochondrial-derived vesicles (MDV), and reduced reactive oxygen species (ROS) production, which supports enhancement of mitochondrial quality control (MQC). Application of SAFit2, an FKBP51 inhibitor, reduced the effects of CCl4-induced liver injury and was associated with increased Parkin, pAKT, and ATP production. Conclusions Downregulation of FKBP51 represents a promising therapeutic target for liver disease treatment. Graphical Abstract

show abstract

“…Post-translational modifications of proteins are a rapid and efficient way to quickly yield proteins with new features demanding relatively little cellular energy [ 55 ]. In the current study, acetylation was the most frequent modification observed in the MS-detected modifications.…”

Section: Discussionmentioning

confidence: 99%

Differential interactome mapping of aggregation prone/prion-like proteins under stress: novel links to stress granule biology

Younas,

Zafar,

Saleem

et al. 2023

Cell Biosci

View full text Add to dashboard Cite

Background Aberrant stress granules (SGs) are emerging as prime suspects in the nucleation of toxic protein aggregates. Understanding the molecular networks linked with aggregation-prone proteins (prion protein, synuclein, and tau) under stressful environments is crucial to understand pathophysiological cascades associated with these proteins. Methods We characterized and validated oxidative stress-induced molecular network changes of endogenous aggregation-prone proteins (prion protein, synuclein, and tau) by employing immunoprecipitation coupled with mass spectrometry analysis under basal and oxidative stress conditions. We used two different cell models (SH-SY5Y: human neuroblastoma and HeLa cell line) to induce oxidative stress using a well-known inducer (sodium arsenite) of oxidative stress. Results Overall, we identified 597 proteins as potential interaction partners. Our comparative interactome mapping provides comprehensive network reorganizations of three aggregation-prone hallmark proteins, establish novel interacting partners and their dysregulation, and validates that prion protein and synuclein localize in cytoplasmic SGs. Localization of prion protein and synuclein in TIA1-positive SGs provides an important link between SG pathobiology and aggregation-prone proteins. In addition, dysregulation (downregulation) of prion protein and exportin-5 protein, and translocation of exportin-5 into the nucleus under oxidative stress shed light on nucleocytoplasmic transport defects during the stress response. Conclusions The current study contributes to our understanding of stress-mediated network rearrangements and posttranslational modifications of prion/prion-like proteins. Localization of prion protein and synuclein in the cytoplasmic SGs provides an important link between stress granule pathobiology and aggregation-prone proteins. In addition, our findings demonstrate nucleocytoplasmic transport defects after oxidative stress via dysregulation and nuclear accumulation of exportin-5.

show abstract

Post-translational modifications and stress adaptation: the paradigm of FKBP51

Cited by 10 publications

References 91 publications

FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin

FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin

Knocking out Fkbp51 decreases CCl4-induced liver injury through enhancement of mitochondrial function and Parkin activity

Differential interactome mapping of aggregation prone/prion-like proteins under stress: novel links to stress granule biology

Contact Info

Product

Resources

About