Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase

C. Liu; M. Poitelea; A. Watson; Shu-hei Yoshida; C. Shimoda; Christian Henrik Holmberg; O. Nielsen; A. M. Carr

doi:10.1038/sj.emboj.7600854

Transactivation of Schizosaccharomyces pombe cdt2⁺ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase

C. Liu, M. Poitelea, A. Watson, Shu-hei Yoshida, C. Shimoda, Christian Henrik Holmberg, O. Nielsen, A. M. Carr

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

84 Citationer (Scopus)

Abstract

Udgivelsesdato: 16 November 2005

Originalsprog	Engelsk
Tidsskrift	EMBO Journal
Vol/bind	24
Sider (fra-til)	3940-3951
ISSN	0261-4189
DOI	https://doi.org/10.1038/sj.emboj.7600854
Status	Udgivet - 2005

Bibliografisk note

Keywords: Cct complex, Cullin, damage checkpoint, ribonucleotide reductase, signalosome

Adgang til dokumentet

10.1038/sj.emboj.7600854

Citationsformater

@article{08bbd1c06c3711dcbee902004c4f4f50,

title = "Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase",

abstract = "Cullin-4 forms a scaffold for multiple ubiquitin ligases. In Schizosaccharomyces pombe, the Cullin-4 homologue (Pcu4) physically associates with Ddb1 and the COP9 signalosome (CSN). One target of this complex is Spd1. Spd1 regulates ribonucleotide reductase (RNR) activity. Spd1 degradation during S phase, or following DNA damage of G2 cells, results in the nuclear export of the small RNR subunit. We demonstrate that Cdt2, an unstable WD40 protein, is a regulatory subunit of Pcu4-Ddb1-CSN ubiquitin ligase. cdt2 deletion stabilises Spd1 and prevents relocalisation of the small RNR subunit from the nucleus to the cytoplasm. cdt2+ is periodically transcribed by the Cdc10/DSC1 transcription factor during S phase and transiently transcribed following DNA damage of G2 cells, corresponding to Spd1 degradation profiles. Cdt2 co-precipitates with Spd1, and Cdt2 overexpression results in constitutive Spd1 degradation. We propose that Cdt2 incorporation into the Pcu4-Ddb1-CSN complex prompts Spd1 targeting and subsequent degradation and that Cdt2 is a WD40 repeat adaptor protein for Cullin-4-based ubiquitin ligase.",

author = "C. Liu and M. Poitelea and A. Watson and Shu-hei Yoshida and C. Shimoda and Holmberg, {Christian Henrik} and O. Nielsen and Carr, {A. M.}",

note = "Keywords: Cct complex, Cullin, damage checkpoint, ribonucleotide reductase, signalosome",

year = "2005",

doi = "10.1038/sj.emboj.7600854",

language = "English",

volume = "24",

pages = "3940--3951",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase

AU - Liu, C.

AU - Poitelea, M.

AU - Watson, A.

AU - Yoshida, Shu-hei

AU - Shimoda, C.

AU - Holmberg, Christian Henrik

AU - Nielsen, O.

AU - Carr, A. M.

N1 - Keywords: Cct complex, Cullin, damage checkpoint, ribonucleotide reductase, signalosome

PY - 2005

Y1 - 2005

N2 - Cullin-4 forms a scaffold for multiple ubiquitin ligases. In Schizosaccharomyces pombe, the Cullin-4 homologue (Pcu4) physically associates with Ddb1 and the COP9 signalosome (CSN). One target of this complex is Spd1. Spd1 regulates ribonucleotide reductase (RNR) activity. Spd1 degradation during S phase, or following DNA damage of G2 cells, results in the nuclear export of the small RNR subunit. We demonstrate that Cdt2, an unstable WD40 protein, is a regulatory subunit of Pcu4-Ddb1-CSN ubiquitin ligase. cdt2 deletion stabilises Spd1 and prevents relocalisation of the small RNR subunit from the nucleus to the cytoplasm. cdt2+ is periodically transcribed by the Cdc10/DSC1 transcription factor during S phase and transiently transcribed following DNA damage of G2 cells, corresponding to Spd1 degradation profiles. Cdt2 co-precipitates with Spd1, and Cdt2 overexpression results in constitutive Spd1 degradation. We propose that Cdt2 incorporation into the Pcu4-Ddb1-CSN complex prompts Spd1 targeting and subsequent degradation and that Cdt2 is a WD40 repeat adaptor protein for Cullin-4-based ubiquitin ligase.

AB - Cullin-4 forms a scaffold for multiple ubiquitin ligases. In Schizosaccharomyces pombe, the Cullin-4 homologue (Pcu4) physically associates with Ddb1 and the COP9 signalosome (CSN). One target of this complex is Spd1. Spd1 regulates ribonucleotide reductase (RNR) activity. Spd1 degradation during S phase, or following DNA damage of G2 cells, results in the nuclear export of the small RNR subunit. We demonstrate that Cdt2, an unstable WD40 protein, is a regulatory subunit of Pcu4-Ddb1-CSN ubiquitin ligase. cdt2 deletion stabilises Spd1 and prevents relocalisation of the small RNR subunit from the nucleus to the cytoplasm. cdt2+ is periodically transcribed by the Cdc10/DSC1 transcription factor during S phase and transiently transcribed following DNA damage of G2 cells, corresponding to Spd1 degradation profiles. Cdt2 co-precipitates with Spd1, and Cdt2 overexpression results in constitutive Spd1 degradation. We propose that Cdt2 incorporation into the Pcu4-Ddb1-CSN complex prompts Spd1 targeting and subsequent degradation and that Cdt2 is a WD40 repeat adaptor protein for Cullin-4-based ubiquitin ligase.

U2 - 10.1038/sj.emboj.7600854

DO - 10.1038/sj.emboj.7600854

M3 - Journal article

C2 - 16252005

SN - 0261-4189

VL - 24

SP - 3940

EP - 3951

JO - EMBO Journal

JF - EMBO Journal

ER -