The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop

Haupt, Katja; Jahreis, Günther; Linnert, Miriam; Maestre-Martínez, Mitcheell; Malešević, Miroslav; Pechstein, Arndt; Edlich, Frank; Lücke, Christian

doi:10.1074/jbc.m111.317214

Cited by 16 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, FKBP38 peptidylprolyl isomerase activity critically depends on complex formation with Ca 2 + /calmodulin [68]. It has been proposed that only the 'active' Ca 2 + /calmodulin-FKBP38 complex can bind Bcl-2 [68], which is consistent with findings that a charge-sensitive loop within the catalytic domain of FKBP38 is responsible for Bcl-2 binding [69]. This provides an interesting link between Ca 2 + signalling and Bcl-2-protein function.…”

Section: Bcl-2 Proteins As Targets Of Immunophilinssupporting

confidence: 53%

Bcl-2 and FKBP12 bind to IP3 and ryanodine receptors at overlapping sites: the complexity of protein–protein interactions for channel regulation

Vervliet

Parys

Bultynck

2015

Biochemical Society Transactions

View full text Add to dashboard Cite

The 12- and 12.6-kDa FK506-binding proteins, FKBP12 (12-kDa FK506-binding protein) and FKBP12.6 (12.6-kDa FK506-binding protein), have been implicated in the binding to and the regulation of ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs), both tetrameric intracellular Ca2+-release channels. Whereas the amino acid sequences responsible for FKBP12 binding to RyRs are conserved in IP3Rs, FKBP12 binding to IP3Rs has been questioned and could not be observed in various experimental models. Nevertheless, conservation of these residues in the different IP3R isoforms and during evolution suggested that they could harbour an important regulatory site critical for IP3R-channel function. Recently, it has become clear that in IP3Rs, this site was targeted by B-cell lymphoma 2 (Bcl-2) via its Bcl-2 homology (BH)4 domain, thereby dampening IP3R-mediated Ca2+ flux and preventing pro-apoptotic Ca2+ signalling. Furthermore, vice versa, the presence of the corresponding site in RyRs implied that Bcl-2 proteins could associate with and regulate RyR channels. Recently, the existence of endogenous RyR-Bcl-2 complexes has been identified in primary hippocampal neurons. Like for IP3Rs, binding of Bcl-2 to RyRs also involved its BH4 domain and suppressed RyR-mediated Ca2+ release. We therefore propose that the originally identified FKBP12-binding site in IP3Rs is a region critical for controlling IP3R-mediated Ca2+ flux by recruiting Bcl-2 rather than FKBP12. Although we hypothesize that anti-apoptotic Bcl-2 proteins, but not FKBP12, are the main physiological inhibitors of IP3Rs, we cannot exclude that Bcl-2 could help engaging FKBP12 (or other FKBP isoforms) to the IP3R, potentially via calcineurin.

show abstract

Section: Bcl-2 Proteins As Targets Of Immunophilinssupporting

confidence: 53%

Bcl-2 and FKBP12 bind to IP3 and ryanodine receptors at overlapping sites: the complexity of protein–protein interactions for channel regulation

Vervliet

Parys

Bultynck

2015

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…FKBP38 mediates neuronal apoptosis ( Maestre-Martinez et al, 2011 ), and FKBP38 −/− mice die soon after birth ( Shirane et al, 2008 ). Th e catalytic domain of FKBP38 binds to Bcl-2 through a charge-sensitive loop ( Haupt et al, 2012 ) to control apoptosis; this interaction is regulated by Ca 2+ and Rheb ( Ma et al, 2010 ; Maestre-Martinez et al, 2011 ; Haupt et al, 2012 ). FKBP38 is associated with many functions, from programmed cell death to the development of the embryo and postnatal brain.…”

Section: Introductionmentioning

confidence: 99%

Direct Interaction between Ras Homolog Enriched in Brain and FK506 Binding Protein 38 in Cashmere Goat Fetal Fibroblast Cells

Wang

Wang²,

et al. 2014

Asian Australas. J. Anim. Sci

View full text Add to dashboard Cite

Ras homolog enriched in brain (Rheb) and FK506 binding protein 38 (FKBP38) are two important regulatory proteins in the mammalian target of rapamycin (mTOR) pathway. There are contradictory data on the interaction between Rheb and FKBP38 in human cells, but this association has not been examined in cashmere goat cells. To investigate the interaction between Rheb and FKBP38, we overexpressed goat Rheb and FKBP38 in goat fetal fibroblasts, extracted whole proteins, and performed coimmunoprecipitation to detect them by western blot. We found Rheb binds directly to FKBP38. Then, we constructed bait vectors (pGBKT7-Rheb/FKBP38) and prey vectors (pGADT7-Rheb/FKBP38), and examined their interaction by yeast two-hybrid assay. Their direct interaction was observed, regardless of which plasmid served as the prey or bait vector. These results indicate that the 2 proteins interact directly in vivo. Novel evidence is presented on the mTOR signal pathway in Cashmere goat cells.

show abstract

“…Recent confocal microscopy results have showed that FKBP8 and NS5A protein of the classical swine fever virus colocalize in the cytoplasm, suggesting a strong interaction between the proteins . Furthermore, RNAi‐mediated silencing of FKBP8 gene can induce the activation of mTOR signaling in goat fetal fibroblasts via protein‐protein interaction through its ankyrin‐repeat domain . FKBP8 can interact with the antiapoptotic protein B‐cell lymphoma 2 (Bcl‐2) and protect it from degradation …”

Section: Discussionmentioning

confidence: 99%

“…14 Furthermore, RNAi-mediated silencing of FKBP8 gene can induce the activation of mTOR signaling in goat fetal fibroblasts via protein-protein interaction through its ankyrin-repeat domain. [30][31][32][33] FKBP8 can interact with the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and protect it from degradation. 34 The spatial localization data between FKBP8 and RIG-I, VISA, and TBK1 indicate that FKBP8 translocates from the cytoplasm to the mitochondrial outer membrane and endoplasmic reticulum membrane to participate in the RLR-VISA signaling pathway and thus plays a crucial role in the antiviral process.…”

Section: Discussionmentioning

confidence: 99%

FKBP8 inhibits virus‐induced RLR‐VISA signaling

Yuan

et al. 2018

Journal of Medical Virology

View full text Add to dashboard Cite

The mitochondrial antiviral signal protein mitochondrial antiviral signaling protein, also known as virus‐induced signaling adaptor (VISA), plays a key role in regulating host innate immune signaling pathways. This study identifies FK506 binding protein 8 (FKBP8) as a candidate interacting protein of VISA through the yeast two‐hybrid technique. The interaction of FKBP8 with VISA, retinoic acid inducible protein 1 (RIG‐I), and IFN regulatory factor 3 (IRF3) was confirmed during viral infection in mammalian cells by coimmunoprecipitation. Overexpression of FKBP8 using a eukaryotic expression plasmid significantly attenuated Sendai virus–induced activation of the promoter interferons β (IFN‐β), and transcription factors nuclear factor κ‐light chain enhancer of activated B cells (NF‐κB) and IFN‐stimulated response element (ISRE). Overexpression of FKBP8 also decreased dimer‐IRF3 activity, but enhanced virus replication. Conversely, knockdown of FKBP8 expression by RNA interference showed opposite effects. Further studies indicated that FKBP8 acts as a negative interacting partner to regulate RLR‐VISA signaling by acting on VISA and TANK binding kinase 1 (TBK1). Additionally, FKBP8 played a negative role on virus‐induced signaling by inhibiting the formation of TBK1‐IRF3 and VISA‐TRAF3 complexes. Notably, FKBP8 also promoted the degradation of TBK1, RIG‐I, and TRAF3 resulting from FKBP8 reinforced Sendai virus–induced endogenous polyubiquitination of RIG‐I, TBK1, and TNF receptor‐associated factor 3 (TRAF3). Therefore, a novel function of FKBP8 in innate immunity antiviral signaling regulation was revealed in this study.

show abstract

The FKBP38 Catalytic Domain Binds to Bcl-2 via a Charge-sensitive Loop

Cited by 16 publications

References 33 publications

Bcl-2 and FKBP12 bind to IP3 and ryanodine receptors at overlapping sites: the complexity of protein–protein interactions for channel regulation

Bcl-2 and FKBP12 bind to IP3 and ryanodine receptors at overlapping sites: the complexity of protein–protein interactions for channel regulation

Direct Interaction between Ras Homolog Enriched in Brain and FK506 Binding Protein 38 in Cashmere Goat Fetal Fibroblast Cells

FKBP8 inhibits virus‐induced RLR‐VISA signaling

Contact Info

Product

Resources

About