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PMID: 12695334 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms.

Genes & development ·Vol. 17 ·No. 9 ·2003-05-01 ·Pages 1130-40

Liu C, Powell KA, Mundt K, Wu L, Carr AM, Caspari T

Abstract

The signalosome is implicated in regulating cullin-dependent ubiquitin ligases. We find that two signalosome subunits, Csn1 and Csn2, are required to regulate ribonucleotide reductase (RNR) through the degradation of a small protein, Spd1, that acts to anchor the small RNR subunit in the nucleus. Spd1 destruction correlates with the nuclear export of the small RNR subunit, which, in turn, correlates with a requirement for RNR in replication and repair. Spd1 degradation is promoted by two separate CSN-dependent mechanisms. During unperturbed S phase, Spd1 degradation is independent of checkpoint proteins. In irradiated G2 cells, Spd1 degradation requires the DNA damage checkpoint. The signalosome copurifies with Pcu4 (cullin 4). Pcu4, Csn1, and Csn2 promote the degradation of Spd1, identifying a new function for the signalosome as a regulator of Pcu4-containing E3 ubiquitin ligase.

MeSH Terms
COP9 Signalosome Complex Cell Cycle Proteins/metabolism Gene Expression Regulation, Fungal/physiology Genes, cdc Multiprotein Complexes Peptide Hydrolases Proteins/metabolism Ribonucleotide Reductases/metabolism Schizosaccharomyces pombe Proteins/metabolism
Chemicals
Cell Cycle Proteins Multiprotein Complexes Proteins Schizosaccharomyces pombe Proteins Spd1 protein, S pombe Ribonucleotide Reductases SUC22 protein, S pombe Peptide Hydrolases COP9 Signalosome Complex
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Liu Cong
Genome Damage and Stability Centre, University of Sussex, Falmer, BN1 9RQ, UK.
Powell Kelly A
Mundt Kirsten
Wu LeJung
Carr Antony M
Caspari Thomas
References (53)
53 references, click to expand
  1. Cullin 4A associates with the UV-damaged DNA-binding protein DDB.
    J Biol Chem. 1999 Dec 10;274(50):35309-12 PMID: 10585395
  2. cdc25+ functions as an inducer in the mitotic control of fission yeast.
    Cell. 1986 Apr 11;45(1):145-53 PMID: 3955656
  3. The COP9/signalosome complex is conserved in fission yeast and has a role in S phase.
    Curr Biol. 1999 Dec 2;9(23):1427-30 PMID: 10607571
  4. Characterization of Schizosaccharomyces pombe Hus1: a PCNA-related protein that associates with Rad1 and Rad9.
    Mol Cell Biol. 2000 Feb;20(4):1254-62 PMID: 10648611
  5. Mik1 levels accumulate in S phase and may mediate an intrinsic link between S phase and mitosis.
    Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2579-84 PMID: 10716991
  6. Unified nomenclature for the COP9 signalosome and its subunits: an essential regulator of development.
    Trends Genet. 2000 May;16(5):202-3 PMID: 10782111
  7. Targeted destabilization of HY5 during light-regulated development of Arabidopsis.
    Nature. 2000 May 25;405(6785):462-6 PMID: 10839542
  8. Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis.
    Mol Cell. 2000 Apr;5(4):737-44 PMID: 10882109
  9. Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast.
    EMBO J. 2000 Jul 3;19(13):3475-84 PMID: 10880460
  10. The Spd1p S phase inhibitor can activate the DNA replication checkpoint pathway in fission yeast.
    J Cell Sci. 2000 Dec;113 Pt 23:4341-50 PMID: 11069778
  11. Vectors and gene targeting modules for tandem affinity purification in Schizosaccharomyces pombe.
    Yeast. 2001 May;18(7):657-62 PMID: 11329175
  12. Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.
    Science. 2001 May 18;292(5520):1382-5 PMID: 11337588
  13. The xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells.
    Mol Cell Biol. 2001 Oct;21(20):6738-47 PMID: 11564859
  14. Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo.
    Mol Cell Biol. 2001 Oct;21(20):6782-95 PMID: 11564863
  15. COP9 signalosome revisited: a novel mediator of protein degradation.
    Trends Cell Biol. 2001 Oct;11(10):420-6 PMID: 11567875
  16. Deletion mutants in COP9/signalosome subunits in fission yeast Schizosaccharomyces pombe display distinct phenotypes.
    Mol Biol Cell. 2002 Feb;13(2):493-502 PMID: 11854407
  17. Arabidopsis COP10 is a ubiquitin-conjugating enzyme variant that acts together with COP1 and the COP9 signalosome in repressing photomorphogenesis.
    Genes Dev. 2002 Mar 1;16(5):554-9 PMID: 11877375
  18. The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1.
    Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3746-51 PMID: 11904430
  19. Two interacting bZIP proteins are direct targets of COP1-mediated control of light-dependent gene expression in Arabidopsis.
    Genes Dev. 2002 May 15;16(10):1247-59 PMID: 12023303
  20. Plant development: regulation by protein degradation.
    Science. 2002 Aug 2;297(5582):793-7 PMID: 12161644
  21. The use of cell division cycle mutants to investigate the control of microtubule distribution in the fission yeast Schizosaccharomyces pombe.
    J Cell Sci. 1988 Mar;89 ( Pt 3):343-57 PMID: 3198697
  22. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
    Methods Enzymol. 1991;194:795-823 PMID: 2005825
  23. 1H NMR studies of mouse ribonucleotide reductase: the R2 protein carboxyl-terminal tail, essential for subunit interaction, is highly flexible but becomes rigid in the presence of protein R1.
    Biochemistry. 1994 Mar 15;33(10):2838-42 PMID: 8130196
  24. A conditional lethal mutant in the fission yeast 26 S protease subunit mts3+ is defective in metaphase to anaphase transition.
    J Biol Chem. 1996 Mar 8;271(10):5704-11 PMID: 8621436
  25. The COP9 complex, a novel multisubunit nuclear regulator involved in light control of a plant developmental switch.
    Cell. 1996 Jul 12;86(1):115-21 PMID: 8689678
  26. Cell cycle, DNA damage and heat shock regulate suc22+ expression in fission yeast.
    Mol Gen Genet. 1996 Sep 13;252(3):284-91 PMID: 8842148
  27. A novel S phase inhibitor in fission yeast.
    EMBO J. 1996 Sep 2;15(17):4603-12 PMID: 8887552
  28. The Schizosaccharomyces pombe rad3 checkpoint gene.
    EMBO J. 1996 Dec 2;15(23):6641-51 PMID: 8978690
  29. Genetic and developmental control of nuclear accumulation of COP1, a repressor of photomorphogenesis in Arabidopsis.
    Plant Physiol. 1997 Jul;114(3):779-88 PMID: 9232869
  30. Analysis of radiation-sensitive mutants of fission yeast.
    Methods Enzymol. 1997;283:471-94 PMID: 9251042
  31. Stress-activated protein kinase pathway in cell cycle control of fission yeast.
    Methods Enzymol. 1997;283:506-20 PMID: 9251044
  32. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.
    Cell. 1997 Oct 17;91(2):209-19 PMID: 9346238
  33. A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p.
    Cell. 1997 Oct 17;91(2):221-30 PMID: 9346239
  34. S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe.
    Genes Dev. 1998 Feb 1;12(3):382-95 PMID: 9450932
  35. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits.
    FASEB J. 1998 Apr;12(6):469-78 PMID: 9535219
  36. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe.
    Yeast. 1998 Jul;14(10):943-51 PMID: 9717240
  37. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway.
    Genes Dev. 1998 Sep 15;12(18):2956-70 PMID: 9744871
  38. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools.
    Mol Cell. 1998 Sep;2(3):329-40 PMID: 9774971
  39. Analysis of Rad3 and Chk1 protein kinases defines different checkpoint responses.
    EMBO J. 1998 Dec 15;17(24):7239-49 PMID: 9857181
  40. Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase.
    Genes Cells. 1998 Nov;3(11):721-35 PMID: 9990507
  41. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.
    Science. 1999 Apr 23;284(5414):657-61 PMID: 10213691
  42. Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1.
    Science. 1999 Apr 23;284(5414):662-5 PMID: 10213692
  43. MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function.
    BMC Biochem. 2002;3:28 PMID: 12370088
  44. De-etiolated 1 and damaged DNA binding protein 1 interact to regulate Arabidopsis photomorphogenesis.
    Curr Biol. 2002 Sep 3;12(17):1462-72 PMID: 12225661
  45. The photomorphogenesis regulator DET1 binds the amino-terminal tail of histone H2B in a nucleosome context.
    Curr Biol. 2002 Sep 3;12(17):1529-34 PMID: 12225670
  46. Multiple ubiquitin ligase-mediated processes require COP9 signalosome and AXR1 function.
    Plant Cell. 2002 Oct;14(10):2553-63 PMID: 12368504
  47. Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1.
    Science. 2002 Oct 18;298(5593):608-11 PMID: 12183637
  48. Characterization of a Schizosaccharomyces pombe strain deleted for a sequence homologue of the human damaged DNA binding 1 (DDB1) gene.
    J Biol Chem. 2002 Oct 25;277(43):41183-91 PMID: 12181326
  49. The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p.
    BMC Biochem. 2001;2:7 PMID: 11504566
  50. Conservation of the COP9/signalosome in budding yeast.
    BMC Genet. 2002 Aug 20;3:15 PMID: 12186635
  51. A simple Cre-loxP method for chromosomal N-terminal tagging of essential and non-essential Schizosaccharomyces pombe genes.
    Gene. 2003 Jan 30;304:133-41 PMID: 12568722
  52. The primary structure of the alcohol dehydrogenase gene from the fission yeast Schizosaccharomyces pombe.
    J Biol Chem. 1983 Jan 10;258(1):143-9 PMID: 6294096
  53. Yeast Sml1, a protein inhibitor of ribonucleotide reductase.
    J Biol Chem. 1999 Dec 17;274(51):36679-83 PMID: 10593972
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1090803
Published
2003-05-01
Epub
2003-00-14
Pages
1130-40
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196048
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1090803 PMC Full Text View journal details
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