Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90

Rebecca A. Sager; Mark R. Woodford; Sarah J. Backe; Alan M. Makedon; Alexander J. Baker-Williams; Bryanna T. DiGregorio; David R. Loiselle; Timothy A. Haystead; Natasha E. Zachara; Chrisostomos Prodromou; Dimitra Bourboulia; Laura S. Schmidt; W. Marston Linehan; Gennady Bratslavsky; Mehdi Mollapour

doi:10.1016/j.celrep.2019.01.018

Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90

Rebecca A. Sager, Mark R. Woodford, Sarah J. Backe, Alan M. Makedon, Alexander J. Baker-Williams, Bryanna T. DiGregorio, David R. Loiselle, Timothy A. Haystead, Natasha E. Zachara, Chrisostomos Prodromou, Dimitra Bourboulia, Laura S. Schmidt, W. Marston Linehan, Gennady Bratslavsky, Mehdi Mollapour

School of Medicine

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Sager et al. show that casein-kinase-2-mediated sequential phosphorylation of the co-chaperone FNIP1 leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients. O-GlcNAcylation antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 ubiquitination and proteasomal degradation.

Original language	English (US)
Pages (from-to)	1344-1356.e5
Journal	Cell Reports
Volume	26
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2019.01.018
State	Published - Jan 29 2019

Keywords

BHD
Birt-Hogg-Dubé syndrome
FNIP1
Hsp90
O-GlcNAcylation
PP5
co-chaperone
folliculin-interacting protein 1
heat shock protein 90
serine/threonine protein phosphatase 5

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2019.01.018

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Sager, R. A., Woodford, M. R., Backe, S. J., Makedon, A. M., Baker-Williams, A. J., DiGregorio, B. T., Loiselle, D. R., Haystead, T. A., Zachara, N. E., Prodromou, C., Bourboulia, D., Schmidt, L. S., Linehan, W. M., Bratslavsky, G., & Mollapour, M. (2019). Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90. Cell Reports, 26(5), 1344-1356.e5. https://doi.org/10.1016/j.celrep.2019.01.018

Sager, RA, Woodford, MR, Backe, SJ, Makedon, AM, Baker-Williams, AJ, DiGregorio, BT, Loiselle, DR, Haystead, TA, Zachara, NE, Prodromou, C, Bourboulia, D, Schmidt, LS, Linehan, WM, Bratslavsky, G & Mollapour, M 2019, 'Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90', Cell Reports, vol. 26, no. 5, pp. 1344-1356.e5. https://doi.org/10.1016/j.celrep.2019.01.018

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title = "Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90",

abstract = "Sager et al. show that casein-kinase-2-mediated sequential phosphorylation of the co-chaperone FNIP1 leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients. O-GlcNAcylation antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 ubiquitination and proteasomal degradation.",

keywords = "BHD, Birt-Hogg-Dub{\'e} syndrome, FNIP1, Hsp90, O-GlcNAcylation, PP5, co-chaperone, folliculin-interacting protein 1, heat shock protein 90, serine/threonine protein phosphatase 5",

author = "Sager, {Rebecca A.} and Woodford, {Mark R.} and Backe, {Sarah J.} and Makedon, {Alan M.} and Baker-Williams, {Alexander J.} and DiGregorio, {Bryanna T.} and Loiselle, {David R.} and Haystead, {Timothy A.} and Zachara, {Natasha E.} and Chrisostomos Prodromou and Dimitra Bourboulia and Schmidt, {Laura S.} and Linehan, {W. Marston} and Gennady Bratslavsky and Mehdi Mollapour",

note = "Funding Information: We thank J. L. Brodsky for the yeast CFTR-HA plasmids and G. Yildirir for cloning OGT-V5 plasmid. This work was supported with funds from the National Institute of General Medical Sciences of the NIH under award number R01GM124256 (M.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also partly supported by the Intramural Research Program of the NIH , National Cancer Institute , Center for Cancer Research; the Frederick National Laboratory for Cancer Research, NIH , under contract HHSN261200800001E (L.S.); SUNY Upstate Medical University , The Upstate Foundation (M.M. and D.B.); the Carol M. Baldwin Breast Cancer Fund (D.B. and M.M.); and the Urology Care Foundation-American Urological Association (M.M.). Publisher Copyright: {\textcopyright} 2019 The Author(s)",

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AU - Woodford, Mark R.

AU - Backe, Sarah J.

AU - Makedon, Alan M.

AU - Baker-Williams, Alexander J.

AU - DiGregorio, Bryanna T.

AU - Loiselle, David R.

AU - Haystead, Timothy A.

AU - Zachara, Natasha E.

AU - Prodromou, Chrisostomos

AU - Bourboulia, Dimitra

AU - Schmidt, Laura S.

AU - Linehan, W. Marston

AU - Bratslavsky, Gennady

AU - Mollapour, Mehdi

N1 - Funding Information: We thank J. L. Brodsky for the yeast CFTR-HA plasmids and G. Yildirir for cloning OGT-V5 plasmid. This work was supported with funds from the National Institute of General Medical Sciences of the NIH under award number R01GM124256 (M.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was also partly supported by the Intramural Research Program of the NIH , National Cancer Institute , Center for Cancer Research; the Frederick National Laboratory for Cancer Research, NIH , under contract HHSN261200800001E (L.S.); SUNY Upstate Medical University , The Upstate Foundation (M.M. and D.B.); the Carol M. Baldwin Breast Cancer Fund (D.B. and M.M.); and the Urology Care Foundation-American Urological Association (M.M.). Publisher Copyright: © 2019 The Author(s)

PY - 2019/1/29

Y1 - 2019/1/29

N2 - Sager et al. show that casein-kinase-2-mediated sequential phosphorylation of the co-chaperone FNIP1 leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients. O-GlcNAcylation antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 ubiquitination and proteasomal degradation.

AB - Sager et al. show that casein-kinase-2-mediated sequential phosphorylation of the co-chaperone FNIP1 leads to incremental inhibition of Hsp90 ATPase activity and gradual activation of both kinase and non-kinase clients. O-GlcNAcylation antagonizes phosphorylation of FNIP1, preventing its interaction with Hsp90, and consequently promotes FNIP1 ubiquitination and proteasomal degradation.

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KW - O-GlcNAcylation

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KW - folliculin-interacting protein 1

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KW - serine/threonine protein phosphatase 5

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Post-translational Regulation of FNIP1 Creates a Rheostat for the Molecular Chaperone Hsp90

Abstract

Keywords

ASJC Scopus subject areas

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