HSP90 is required for TAK1 stability but not for its activation in the pro-inflammatory signaling pathway |
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| Authors: | Xin Yu Liu |
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| Affiliation: | Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore |
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| Abstract: | The protein kinase transforming-growth-factor-β-activated kinase-1 (TAK1) is a key regulator in the pro-inflammatory signaling pathway and is activated by tumor necrosis factor-α, interleukin-1 (IL-1) and lipopolysaccharide (LPS). We describe the identification of TAK1 as a client protein of the 90 kDa heat-shock protein (Hsp90)/cell division cycle protein 37 (Cdc37) chaperones. However, Hsp90 is not required for the activation of TAK1 as short exposure to the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) did not affect its activation by LPS or IL-1. Prolonged treatment of cells with 17-AAG inhibits Hsp90 and downregulates TAK1. Our results suggest that Hsp90 is required for the folding and stability of TAK1 but is displaced and no longer required when TAK1 is complexed to TAK1-binding protein-1 (TAB1).Structured summary- MINT-6797182:
- TAK1 (uniprotkb:O43318-2) physically interacts (MI:0218) with CDC37 (uniprotkb:Q16543) and HSP90 (uniprotkb:P07900) by anti bait coimmunoprecipitation (MI:0006)
- MINT-6797194:
- TAK1 (uniprotkb:O43318-2) physically interacts (MI:0218) with TAB1 (uniprotkb:Q15750), HSP90 (uniprotkb:P07900) and CDC37 (uniprotkb:Q16543) by anti bait coimmunoprecipitation (MI:0006)
- MINT-6797248:
- TAK1 (uniprotkb:Q62073) physically interacts (MI:0218) with HSP90 (uniprotkb:P07901), CDC37 (uniprotkb:Q61081), TAB2 (uniprotkb:Q99K90) and TAB1 (uniprotkb:Q8CF89) by anti bait coimmunoprecipitation (MI:0006)
- MINT-6797232:
- TAK1 (uniprotkb:O43318-2) physically interacts (MI:0218) with HSP90 (uniprotkb:P07900) and CDC37 (uniprotkb:Q16543) by pull down (MI:0096)
- MINT-6797216:
- TAK1 (uniprotkb:O43318-2) physically interacts (MI:0218) with TAB2 (uniprotkb:Q9NYJ8), CDC37 (uniprotkb:Q16543), HSP90 (uniprotkb:P07900) and TAB1 (uniprotkb:Q15750) by anti bait coimmunoprecipitation (MI:0006)
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| Keywords: | 17-AAG, 17-(allylamino)-17-demethoxygeldanamycin Cdc37, cell division cycle protein 37 CUE, coupling of ubiquitin conjugation to endoplasmic reticulum degradation DMEM, Dulbecco&rsquo s modified Eagle&rsquo s medium ELISA, enzyme-linked immunosorbent assay FCS, foetal-calf serum GST, glutathione S-transferase HA, haemagglutinin HEK293, human embryonic kidney 293 cells Hsp90, 90 kDa heat-shock protein IκB, inhibitor of NF-κB IKK, inhibitor of nuclear factor κB kinase IL, interleukin IRAK, interleukin-1 receptor-associated kinase JNK, c-Jun N-terminal kinase LPS, lipopolysaccharide MAPK, mitogen-activated protein kinase MKK, MAP kinase kinase MyD88, myeloid differentiation factor 88 NF-κB, nuclear factor κB RIP, receptor-interacting protein TAB, TAK1-binding protein TAK1, transforming-growth-factor-β-activated kinase-1 TNF, tumor necrosis factor TRADD, TNF receptor-associated death domain TRAF, TNF-receptor-associated factor Ubc13, ubiquitin-conjugating enzyme 13 Uev1A, ubiquitin E2 variant 1a |
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