PAWS1 controls Wnt signalling through association with casein kinase 1α

Polyxeni Bozatzi; Kevin S. Dingwell; Kevin Z. L. Wu; Fay Cooper; Timothy D. Cummins; Luke D. Hutchinson; Janis Vogt; Nicola T. Wood; Thomas J. Macartney; Joby Varghese; Robert Gourlay; David G. Campbell; James C. Smith; Gopal P. Sapkota

doi:10.15252/embr.201744807

PAWS1 controls Wnt signalling through association with casein kinase 1α

Polyxeni Bozatzi, Kevin S. Dingwell, Kevin Z. L. Wu, Fay Cooper, Timothy D. Cummins, Luke D. Hutchinson, Janis Vogt, Nicola T. Wood, Thomas J. Macartney, Joby Varghese, Robert Gourlay, David G. Campbell, James C. Smith (Lead / Corresponding author), Gopal P. Sapkota (Lead / Corresponding author)

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Abstract

The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co-localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.

Original language	English
Article number	e44807
Pages (from-to)	1-18
Number of pages	18
Journal	EMBO Reports
Volume	19
Issue number	4
Early online date	7 Mar 2018
DOIs	https://doi.org/10.15252/embr.201744807
Publication status	Published - 1 Apr 2018

Keywords

BMP
CK1
FAM83G
PAWS1
Wnt

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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10.15252/embr.201744807Licence: CC BY

Final Published VersionFinal published version, 4.53 MBLicence: CC BY

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Bozatzi, P., Dingwell, K. S., Wu, K. Z. L., Cooper, F., Cummins, T. D., Hutchinson, L. D., Vogt, J., Wood, N. T., Macartney, T. J., Varghese, J., Gourlay, R., Campbell, D. G., Smith, J. C., & Sapkota, G. P. (2018). PAWS1 controls Wnt signalling through association with casein kinase 1α. EMBO Reports, 19(4), 1-18. Article e44807. https://doi.org/10.15252/embr.201744807

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title = "PAWS1 controls Wnt signalling through association with casein kinase 1α",

abstract = "The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co-localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.",

keywords = "BMP, CK1, FAM83G, PAWS1, Wnt",

author = "Polyxeni Bozatzi and Dingwell, {Kevin S.} and Wu, {Kevin Z. L.} and Fay Cooper and Cummins, {Timothy D.} and Hutchinson, {Luke D.} and Janis Vogt and Wood, {Nicola T.} and Macartney, {Thomas J.} and Joby Varghese and Robert Gourlay and Campbell, {David G.} and Smith, {James C.} and Sapkota, {Gopal P.}",

note = "Funding: RCUK | Medical Research Council (MRC) MC_UU_12016/3FC001157; Wellcome FC001157; Cancer Research UK (CRUK) FC001157; Francis Crick Institute",

year = "2018",

month = apr,

day = "1",

doi = "10.15252/embr.201744807",

language = "English",

volume = "19",

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journal = "EMBO Reports",

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AU - Bozatzi, Polyxeni

AU - Dingwell, Kevin S.

AU - Wu, Kevin Z. L.

AU - Cooper, Fay

AU - Cummins, Timothy D.

AU - Hutchinson, Luke D.

AU - Vogt, Janis

AU - Wood, Nicola T.

AU - Macartney, Thomas J.

AU - Varghese, Joby

AU - Gourlay, Robert

AU - Campbell, David G.

AU - Smith, James C.

AU - Sapkota, Gopal P.

N1 - Funding: RCUK | Medical Research Council (MRC) MC_UU_12016/3FC001157; Wellcome FC001157; Cancer Research UK (CRUK) FC001157; Francis Crick Institute

PY - 2018/4/1

Y1 - 2018/4/1

N2 - The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co-localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.

AB - The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co-localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in Xenopus embryos.

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KW - CK1

KW - FAM83G

KW - PAWS1

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DO - 10.15252/embr.201744807

M3 - Article

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EP - 18

JO - EMBO Reports

JF - EMBO Reports

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M1 - e44807

ER -

PAWS1 controls Wnt signalling through association with casein kinase 1α

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Elucidating the biological function of the uncharacterised protein FAM83G/PAWS1: Role in Wnt signalling through its interaction with Caseine Kinase 1α

Identification of novel protein kinase regulators of TGFβ signalling

Sapkota, Gopal

Cite this

PAWS1 controls Wnt signalling through association with casein kinase 1α

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Student theses

Elucidating the biological function of the uncharacterised protein FAM83G/PAWS1: Role in Wnt signalling through its interaction with Caseine Kinase 1α

Identification of novel protein kinase regulators of TGFβ signalling

Profiles

Sapkota, Gopal

Cite this