FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance

Pereira, Maria J.; Palming, Jenny; Svensson, Maria; Rizell, Magnus; Dalenbäck, Jan; Hammar, Mårten; Fall, Tove; Sidibeh, Cherno O.; Svensson, Per‐Arne; Eriksson, Jan W.

doi:10.1016/j.metabol.2014.05.015

Cited by 81 publications

(120 citation statements)

References 51 publications

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“…Furthermore, in conjunction with insulin resistance markers, FKBP51, as a steroid hormone responsive and regulatory gene, demonstrated an increase in the expression, following dexamethasone exposure 85 .…”

Section: The Role Of Ppiases In T2dmentioning

confidence: 98%

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The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

McClements¹,

Annett²,

Yakkundi³

et al. 2015

CMP

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Peptidyl prolyl isomerases (PPIases) are proteins belonging to the immunophilin family and are characterised by their cis-trans isomerization activity at the X-Pro peptide bond, in addition to their tetratricopeptide repeat (TPR) domain, important for interaction with the molecular chaperone, Hsp90. Due to this unique structure these proteins are able to facilitate proteinprotein interactions which can impact significantly on a range of cellular processes such as cell signalling, differentiation, cell cycle progression, metabolic activity and apoptosis.Malfunction and/or dysregulation of most members of this class of proteins promotes cellular damage and tissue/organ failure, predisposing to ageing and age-related diseases. Many individual genes within the PPIase family are associated with several age-related diseases including cardiovascular diseases (CVDs), atherosclerosis, type II diabetes (T2D), chronic kidney disease (CDK), neurodegeneration, cancer and age-related macular degeneration (AMD), in addition to the ageing process itself. This review will focus on the different roles of PPIases, and their therapeutic/biomarker potential in these age-related vascular diseases.

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Section: The Role Of Ppiases In T2dmentioning

confidence: 98%

“…For example, FKBP51 SNPs were found to be associated with T2D phenotypes in large population studies 85 . Also, the change in FKBP51 gene expression was demonstrated in response to stress and diet therefore indicating a correlation between FKBP51 levels and higher food intake.…”

Section: The Role Of Ppiases In T2dmentioning

confidence: 99%

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

McClements¹,

Annett²,

Yakkundi³

et al. 2015

CMP

View full text Add to dashboard Cite

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“…Therefore, FKBP5 represents a novel target in metabolic regulation. It has been reported that ATP or certain concentrations of statins activate PHLPP isoforms along with other phosphatases and regulate signaling patterns (Pereira et al 2014). On a deeper note, the activation of phosphatases depends upon the factors that regulate cell cycle.…”

Section: Targeting the Critical Phlpp-akt Interaction: Role Of Scaffomentioning

confidence: 99%

“…On a deeper note, the activation of phosphatases depends upon the factors that regulate cell cycle. So, higher FKBP5 gene expression is observed in adipose tissue and is associated with reduced insulin effects on glucose uptake (Pereira et al 2014). Furthermore, its gene expression in subcutaneous adipose tissue positively correlates with serum insulin, adipocyte diameter and negatively with plasma HDLcholesterol, thereby implicating its possible potential role in insulin resistance.…”

Section: Targeting the Critical Phlpp-akt Interaction: Role Of Scaffomentioning

confidence: 99%

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PHLPP: a putative cellular target during insulin resistance and type 2 diabetes

Mathur

Pandey

Kakkar

2017

Journal of Endocrinology

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Progressive research in the past decade converges to the impact of PHLPP in regulating the cellular metabolism through PI3K/AKT inhibition. Aberrations in PKB/AKT signaling coordinates with impaired insulin secretion and insulin resistance, identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we discuss the impact of PHLPP isoforms in insulin signaling and its associated cellular events including mitochondrial dysfunction, DNA damage, autophagy and cell death. The article highlights the plausible molecular targets that share the role during insulin-resistant states, whose understanding can be extended into treatment responses to facilitate targeted drug discovery for T2D and allied metabolic syndromes.

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Entdeckung eines potenten PROTAC ermöglicht die gezielte Ausschaltung der Gerüstfunktionen von FKBP51

Geiger,

Walz,

Meyners

et al. 2023

Angewandte Chemie

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Das FK506‐bindende Protein 51 (FKBP51) stellt ein vielversprechendes Wirkstoffziel zur Behandlung von verschiedenen Krankheiten dar, darunter Depression, chronischer Schmerz und Fettleibigkeit. Bisherige FKBP51‐gerichtete Wirkstoffe waren auf die Blockade der FK506‐Bindestelle beschränkt, wodurch Kernfunktionen von FKBP51 jedoch nicht beeinträchtigt werden. Hier präsentieren wir die Entwicklung des ersten FKBP51 Proteolysis Targeting Chimeras (PROTAC), der den Abbau von FKBP51 ermöglicht und damit auch die Gerüstfunktion von FKBP51 ausschalten kann. Die initiale Synthese von 220 FKBP‐gerichteten PROTACs ergab eine Vielzahl aktiver PROTACs für FKBP12, sechs für FKBP51 und keinen für FKBP52. Die Strukturanalyse eines binären FKBP12:PROTAC‐Komplexes offenbarte die molekulare Grundlage für negative Kooperativität. Die Linker‐Optimierung eines FKBP51 PROTACs der ersten Generation führte zur Entwicklung von SelDeg51 mit verbesserter zellulärer Aktivität, Selektivität und hoher Kooperativität. Die Struktur des ternären FKBP51:SelDeg51:VCB Komplexes zeigte, wie SelDeg51 durch Dimerisierung von FKBP51 und VHL Kooperativität herstellt, die dem Bindungsmodus von molekularen Klebern ähnelt. SelDeg51 baut FKBP51 auf effiziente Weise in Zellen ab und reaktiviert den GR‐Signalweg, was die erhöhte Wirksamkeit des Proteinabbaus im Vergleich zur klassischen FKBP51‐Besetzung demonstriert.

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FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance

Cited by 81 publications

References 51 publications

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

PHLPP: a putative cellular target during insulin resistance and type 2 diabetes

Entdeckung eines potenten PROTAC ermöglicht die gezielte Ausschaltung der Gerüstfunktionen von FKBP51

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