The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms

Luke Fulcher, Polyxeni Bozatzi, Theresa Tachie-Menson, Kevin Wu, Timothy D. Cummins, Joshua C. Bufton, Daniel M. Pinkas, Karen Dunbar, Sabin Shrestha, Nicola Wood, Simone Weidlich, Thomas Macartney, Joby Varghese, Robert Gourlay, David Campbell, Kevin S. Dingwell, James C. Smith, Alex N. Bullock, Gopal Sapkota (Lead / Corresponding author)

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Abstract

Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain.
Original languageEnglish
Article numbereaao2341
JournalScience Signaling
Volume11
Issue number531
DOIs
Publication statusPublished - 22 May 2018

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Casein Kinase I
Anchors
Protein Isoforms
Proteins
Protein-Serine-Threonine Kinases
Circadian Rhythm
Proteolysis
Assays
Cell Cycle
Phosphotransferases
Cells

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Fulcher, Luke ; Bozatzi, Polyxeni ; Tachie-Menson, Theresa ; Wu, Kevin ; Cummins, Timothy D. ; Bufton, Joshua C. ; Pinkas, Daniel M. ; Dunbar, Karen ; Shrestha, Sabin ; Wood, Nicola ; Weidlich, Simone ; Macartney, Thomas ; Varghese, Joby ; Gourlay, Robert ; Campbell, David ; Dingwell, Kevin S. ; Smith, James C. ; Bullock, Alex N. ; Sapkota, Gopal. / The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms. In: Science Signaling. 2018 ; Vol. 11, No. 531.
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title = "The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms",
abstract = "Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain.",
author = "Luke Fulcher and Polyxeni Bozatzi and Theresa Tachie-Menson and Kevin Wu and Cummins, {Timothy D.} and Bufton, {Joshua C.} and Pinkas, {Daniel M.} and Karen Dunbar and Sabin Shrestha and Nicola Wood and Simone Weidlich and Thomas Macartney and Joby Varghese and Robert Gourlay and David Campbell and Dingwell, {Kevin S.} and Smith, {James C.} and Bullock, {Alex N.} and Gopal Sapkota",
note = "Funding: LJF, PB, TT-M are supported by the U.K. MRC PhD studentships. The Dundee Imaging Facility, which provided image analysis support, is funded by the 'MRC Next Generation Optical Microscopy' award [MR/K015869/1]. LJF also receives funding from the Queens College Scholarship, University of Dundee. KW and KD are supported by MRC Career Development Fellowships. GPS is supported by the U.K. Medical Research Council (grant number MC_UU_12016/3) and the pharmaceutical companies supporting the DSTT (Boehringer-Ingelheim, GlaxoSmithKline, Merck-Serono). JCS and KSD are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001157), the UK Medical Research Council (FC001157), and the Wellcome Trust (FC001157). ANB, JCB and DMP are supported by the SGC, which is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, MSD, Merck KGaA, Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, S{\~a}o Paulo Research Foundation-FAPESP, Takeda and Wellcome [106169/ZZ14/Z].",
year = "2018",
month = "5",
day = "22",
doi = "10.1126/scisignal.aao2341",
language = "English",
volume = "11",
journal = "Science Signaling",
issn = "1937-9145",
publisher = "American Association for the Advancement of Science",
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Fulcher, L, Bozatzi, P, Tachie-Menson, T, Wu, K, Cummins, TD, Bufton, JC, Pinkas, DM, Dunbar, K, Shrestha, S, Wood, N, Weidlich, S, Macartney, T, Varghese, J, Gourlay, R, Campbell, D, Dingwell, KS, Smith, JC, Bullock, AN & Sapkota, G 2018, 'The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms', Science Signaling, vol. 11, no. 531, eaao2341. https://doi.org/10.1126/scisignal.aao2341

The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms. / Fulcher, Luke; Bozatzi, Polyxeni; Tachie-Menson, Theresa; Wu, Kevin; Cummins, Timothy D.; Bufton, Joshua C.; Pinkas, Daniel M.; Dunbar, Karen; Shrestha, Sabin; Wood, Nicola; Weidlich, Simone; Macartney, Thomas; Varghese, Joby; Gourlay, Robert; Campbell, David; Dingwell, Kevin S.; Smith, James C.; Bullock, Alex N.; Sapkota, Gopal (Lead / Corresponding author).

In: Science Signaling, Vol. 11, No. 531, eaao2341, 22.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The DUF1669 domain of FAM83 family proteins anchor casein kinase 1 isoforms

AU - Fulcher, Luke

AU - Bozatzi, Polyxeni

AU - Tachie-Menson, Theresa

AU - Wu, Kevin

AU - Cummins, Timothy D.

AU - Bufton, Joshua C.

AU - Pinkas, Daniel M.

AU - Dunbar, Karen

AU - Shrestha, Sabin

AU - Wood, Nicola

AU - Weidlich, Simone

AU - Macartney, Thomas

AU - Varghese, Joby

AU - Gourlay, Robert

AU - Campbell, David

AU - Dingwell, Kevin S.

AU - Smith, James C.

AU - Bullock, Alex N.

AU - Sapkota, Gopal

N1 - Funding: LJF, PB, TT-M are supported by the U.K. MRC PhD studentships. The Dundee Imaging Facility, which provided image analysis support, is funded by the 'MRC Next Generation Optical Microscopy' award [MR/K015869/1]. LJF also receives funding from the Queens College Scholarship, University of Dundee. KW and KD are supported by MRC Career Development Fellowships. GPS is supported by the U.K. Medical Research Council (grant number MC_UU_12016/3) and the pharmaceutical companies supporting the DSTT (Boehringer-Ingelheim, GlaxoSmithKline, Merck-Serono). JCS and KSD are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001157), the UK Medical Research Council (FC001157), and the Wellcome Trust (FC001157). ANB, JCB and DMP are supported by the SGC, which is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, MSD, Merck KGaA, Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda and Wellcome [106169/ZZ14/Z].

PY - 2018/5/22

Y1 - 2018/5/22

N2 - Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain.

AB - Members of the casein kinase 1 (CK1) family of serine-threonine protein kinases are implicated in the regulation of many cellular processes, including the cell cycle, circadian rhythms, and Wnt and Hedgehog signaling. Because these kinases exhibit constitutive activity in biochemical assays, it is likely that their activity in cells is controlled by subcellular localization, interactions with inhibitory proteins, targeted degradation, or combinations of these mechanisms. We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A to FAM83H) interacted with the α and α-like isoforms of CK1; FAM83A, FAM83B, FAM83E, and FAM83H also interacted with the δ and ε isoforms of CK1. We detected no interaction between any FAM83 member and the related CK1γ1, CK1γ2, and CK1γ3 isoforms. Each FAM83 protein exhibited a distinct pattern of subcellular distribution and colocalized with the CK1 isoform(s) to which it bound. The interaction of FAM83 proteins with CK1 isoforms was mediated by the conserved domain of unknown function 1669 (DUF1669) that characterizes the FAM83 family. Mutations in FAM83 proteins that prevented them from binding to CK1 interfered with the proper subcellular localization and cellular functions of both the FAM83 proteins and their CK1 binding partners. On the basis of its function, we propose that DUF1669 be renamed the polypeptide anchor of CK1 domain.

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DO - 10.1126/scisignal.aao2341

M3 - Article

VL - 11

JO - Science Signaling

JF - Science Signaling

SN - 1937-9145

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