RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response

Sara L Poulsen; Rebecca K Hansen; Sebastian A Wagner; Loes van Cuijk; Gijsbert J van Belle; Werner Streicher; Mats Wikström; Chuna Ram Choudhary; Adriaan B Houtsmuller; Jurgen A Marteijn; Simon Bekker-Jensen; Niels Mailand

doi:10.1083/jcb.201212075

RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response

Sara L Poulsen, Rebecca K Hansen, Sebastian A Wagner, Loes van Cuijk, Gijsbert J van Belle, Werner Streicher, Mats Wikström, Chuna Ram Choudhary, Adriaan B Houtsmuller, Jurgen A Marteijn, Simon Bekker-Jensen, Niels Mailand

97 Citations (Scopus)

Abstract

Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified. We show that human RNF111/Arkadia is a new STUbL, which used three adjacent SIMs for specific recognition of poly-SUMO2/3 chains, and used Ubc13-Mms2 as a cognate E2 enzyme to promote nonproteolytic, K63-linked ubiquitylation of SUMOylated target proteins. We demonstrate that RNF111 promoted ubiquitylation of SUMOylated XPC (xeroderma pigmentosum C) protein, a central DNA damage recognition factor in nucleotide excision repair (NER) extensively regulated by ultraviolet (UV)-induced SUMOylation and ubiquitylation. Moreover, we show that RNF111 facilitated NER by regulating the recruitment of XPC to UV-damaged DNA. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response.

Original language	English
Journal	Journal of Cell Biology
Volume	201
Issue number	6
Pages (from-to)	797-807
Number of pages	11
ISSN	0021-9525
DOIs	https://doi.org/10.1083/jcb.201212075
Publication status	Published - 10 Jun 2013

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Poulsen, S. L., Hansen, R. K., Wagner, S. A., van Cuijk, L., van Belle, G. J., Streicher, W., Wikström, M., Choudhary, C. R., Houtsmuller, A. B., Marteijn, J. A., Bekker-Jensen, S., & Mailand, N. (2013). RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response. Journal of Cell Biology, 201(6), 797-807. https://doi.org/10.1083/jcb.201212075

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title = "RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response",

abstract = "Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified. We show that human RNF111/Arkadia is a new STUbL, which used three adjacent SIMs for specific recognition of poly-SUMO2/3 chains, and used Ubc13-Mms2 as a cognate E2 enzyme to promote nonproteolytic, K63-linked ubiquitylation of SUMOylated target proteins. We demonstrate that RNF111 promoted ubiquitylation of SUMOylated XPC (xeroderma pigmentosum C) protein, a central DNA damage recognition factor in nucleotide excision repair (NER) extensively regulated by ultraviolet (UV)-induced SUMOylation and ubiquitylation. Moreover, we show that RNF111 facilitated NER by regulating the recruitment of XPC to UV-damaged DNA. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response.",

author = "Poulsen, {Sara L} and Hansen, {Rebecca K} and Wagner, {Sebastian A} and {van Cuijk}, Loes and {van Belle}, {Gijsbert J} and Werner Streicher and Mats Wikstr{\"o}m and Choudhary, {Chuna Ram} and Houtsmuller, {Adriaan B} and Marteijn, {Jurgen A} and Simon Bekker-Jensen and Niels Mailand",

year = "2013",

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doi = "10.1083/jcb.201212075",

language = "English",

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T1 - RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response

AU - Poulsen, Sara L

AU - Hansen, Rebecca K

AU - Wagner, Sebastian A

AU - van Cuijk, Loes

AU - van Belle, Gijsbert J

AU - Streicher, Werner

AU - Wikström, Mats

AU - Choudhary, Chuna Ram

AU - Houtsmuller, Adriaan B

AU - Marteijn, Jurgen A

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

PY - 2013/6/10

Y1 - 2013/6/10

N2 - Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified. We show that human RNF111/Arkadia is a new STUbL, which used three adjacent SIMs for specific recognition of poly-SUMO2/3 chains, and used Ubc13-Mms2 as a cognate E2 enzyme to promote nonproteolytic, K63-linked ubiquitylation of SUMOylated target proteins. We demonstrate that RNF111 promoted ubiquitylation of SUMOylated XPC (xeroderma pigmentosum C) protein, a central DNA damage recognition factor in nucleotide excision repair (NER) extensively regulated by ultraviolet (UV)-induced SUMOylation and ubiquitylation. Moreover, we show that RNF111 facilitated NER by regulating the recruitment of XPC to UV-damaged DNA. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response.

AB - Protein modifications by ubiquitin and small ubiquitin-like modifier (SUMO) play key roles in cellular signaling pathways. SUMO-targeted ubiquitin ligases (STUbLs) directly couple these modifications by selectively recognizing SUMOylated target proteins through SUMO-interacting motifs (SIMs), promoting their K48-linked ubiquitylation and degradation. Only a single mammalian STUbL, RNF4, has been identified. We show that human RNF111/Arkadia is a new STUbL, which used three adjacent SIMs for specific recognition of poly-SUMO2/3 chains, and used Ubc13-Mms2 as a cognate E2 enzyme to promote nonproteolytic, K63-linked ubiquitylation of SUMOylated target proteins. We demonstrate that RNF111 promoted ubiquitylation of SUMOylated XPC (xeroderma pigmentosum C) protein, a central DNA damage recognition factor in nucleotide excision repair (NER) extensively regulated by ultraviolet (UV)-induced SUMOylation and ubiquitylation. Moreover, we show that RNF111 facilitated NER by regulating the recruitment of XPC to UV-damaged DNA. Our findings establish RNF111 as a new STUbL that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response.

U2 - 10.1083/jcb.201212075

DO - 10.1083/jcb.201212075

M3 - Journal article

C2 - 23751493

SN - 0021-9525

VL - 201

SP - 797

EP - 807

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 6

ER -

RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response

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