Home LiteratureArticle Details
PMID: 12629039 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The RAG1 N-terminal domain is an E3 ubiquitin ligase.

Genes & development ·Vol. 17 ·No. 5 ·2003-03-01 ·Pages 581-5

Yurchenko V, Xue Z, Sadofsky M

Abstract

RAG1 and RAG2 initiate V(D)J recombination, which is the assembly of immunoglobulin and T cell receptor genes. The N-terminal region of RAG1 can be deleted, leaving an enzymatic "core" able to catalyze the complete reaction. Here we report that the N-terminal portion of RAG1 has a distinct enzymatic role separate from the rest of the protein. It acts as an E3 ligase in the ubiquitylation of a test substrate and formation of polyubiquitin chains in vitro. This finding suggests a new way in which V(D)J recombination can be regulated and coupled to other aspects of cell physiology.

MeSH Terms
Animals Gene Rearrangement/physiology Homeodomain Proteins/chemistry,genetics,metabolism Immunoglobulin Variable Region/genetics Ligases/metabolism Mice Protein Structure, Tertiary/genetics,physiology Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases
Chemicals
Homeodomain Proteins Immunoglobulin Variable Region RAG-1 protein UBE2C protein, human Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yurchenko Vyacheslav
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Xue Zhu
Sadofsky Moshe
References (33)
33 references, click to expand
  1. RAG2 is down-regulated by cytoplasmic sequestration and ubiquitin-dependent degradation.
    J Biol Chem. 2002 Nov 1;277(44):41423-7 PMID: 12205088
  2. A RAG-1/RAG-2 tetramer supports 12/23-regulated synapsis, cleavage, and transposition of V(D)J recombination signals.
    Mol Cell Biol. 2002 Nov;22(22):7790-801 PMID: 12391148
  3. Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains.
    EMBO J. 2002 Dec 16;21(24):6755-62 PMID: 12485996
  4. RING finger ubiquitin protein ligases: implications for tumorigenesis, metastasis and for molecular targets in cancer.
    Semin Cancer Biol. 2003 Feb;13(1):5-14 PMID: 12507552
  5. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
    Science. 1990 Jun 22;248(4962):1517-23 PMID: 2360047
  6. Dispensable sequence motifs in the RAG-1 and RAG-2 genes for plasmid V(D)J recombination.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6100-4 PMID: 8327489
  7. Expression and V(D)J recombination activity of mutated RAG-1 proteins.
    Nucleic Acids Res. 1993 Dec 11;21(24):5644-50 PMID: 8284210
  8. Definition of a core region of RAG-2 that is functional in V(D)J recombination.
    Nucleic Acids Res. 1994 May 25;22(10):1805-9 PMID: 8208603
  9. Analysis of regions of RAG-2 important for V(D)J recombination.
    Nucleic Acids Res. 1994 May 25;22(10):1810-4 PMID: 8208604
  10. Regions of RAG1 protein critical for V(D)J recombination.
    Eur J Immunol. 1996 Apr;26(4):886-91 PMID: 8625984
  11. A zinc-binding domain involved in the dimerization of RAG1.
    J Mol Biol. 1996 Jul 5;260(1):70-84 PMID: 8676393
  12. A basic motif in the N-terminal region of RAG1 enhances V(D)J recombination activity.
    Mol Cell Biol. 1997 Aug;17(8):4544-52 PMID: 9234712
  13. Dual role of RAG2 in V(D)J recombination: catalysis and regulation of ordered Ig gene assembly.
    EMBO J. 1998 Aug 17;17(16):4881-6 PMID: 9707447
  14. Roles of the "dispensable" portions of RAG-1 and RAG-2 in V(D)J recombination.
    Mol Cell Biol. 1999 Apr;19(4):3010-7 PMID: 10082568
  15. A RAG1 and RAG2 tetramer complex is active in cleavage in V(D)J recombination.
    Mol Cell Biol. 1999 Jul;19(7):4664-71 PMID: 10373515
  16. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination.
    Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11364-9 PMID: 10500182
  17. The U box is a modified RING finger - a common domain in ubiquitination.
    Curr Biol. 2000 Feb 24;10(4):R132-4 PMID: 10704423
  18. The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases.
    Trends Cell Biol. 2000 Oct;10(10):429-39 PMID: 10998601
  19. N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14572-7 PMID: 11121059
  20. Hrd1p/Der3p is a membrane-anchored ubiquitin ligase required for ER-associated degradation.
    Nat Cell Biol. 2001 Jan;3(1):24-9 PMID: 11146622
  21. A C-terminal region of RAG1 contacts the coding DNA during V(D)J recombination.
    Mol Cell Biol. 2001 Mar;21(6):2038-47 PMID: 11238939
  22. Themes and variations on ubiquitylation.
    Nat Rev Mol Cell Biol. 2001 Mar;2(3):169-78 PMID: 11265246
  23. The RAG proteins in V(D)J recombination: more than just a nuclease.
    Nucleic Acids Res. 2001 Apr 1;29(7):1399-409 PMID: 11266539
  24. Functional organization of single and paired V(D)J cleavage complexes.
    Mol Cell Biol. 2001 Jul;21(13):4256-64 PMID: 11390654
  25. A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Matalpha2 repressor degradation.
    Genes Dev. 2001 Oct 15;15(20):2660-74 PMID: 11641273
  26. Assembly of the RAG1/RAG2 synaptic complex.
    Mol Cell Biol. 2002 Jan;22(1):69-77 PMID: 11739723
  27. Histone ubiquitination: a tagging tail unfolds?
    Bioessays. 2002 Feb;24(2):166-74 PMID: 11835281
  28. The mechanism and regulation of chromosomal V(D)J recombination.
    Cell. 2002 Apr;109 Suppl:S45-55 PMID: 11983152
  29. V(D)J recombination: RAG proteins, repair factors, and regulation.
    Annu Rev Biochem. 2002;71:101-32 PMID: 12045092
  30. Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase.
    J Biol Chem. 2002 Jun 14;277(24):22085-92 PMID: 11927591
  31. Ordered assembly of the V(D)J synaptic complex ensures accurate recombination.
    EMBO J. 2002 Aug 1;21(15):4162-71 PMID: 12145216
  32. Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination.
    Genes Dev. 2002 Aug 1;16(15):1934-49 PMID: 12154124
  33. The "dispensable" portion of RAG2 is necessary for efficient V-to-DJ rearrangement during B and T cell development.
    Immunity. 2002 Nov;17(5):639-51 PMID: 12433370
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1058103
Published
2003-03-01
Pages
581-5
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196008
Subset
IM
Grants
NIAID NIH HHS · R01 AI041711 · United States
NIAID NIH HHS · R29 AI041711 · United States
NIAID NIH HHS · AI41711 · United States
External Links
PubMed source DOI: 10.1101/gad.1058103 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2