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14-3-3 adaptor proteins recruit AID to 5′-AGCT-3′–rich switch regions for class switch recombination

Nature Structural & Molecular Biology volume 17, pages 1124–1135 (2010)Cite this article

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Abstract

Class switch DNA recombination (CSR) is the mechanism that diversifies the biological effector functions of antibodies. Activation-induced cytidine deaminase (AID), a key protein in CSR, targets immunoglobulin H (IgH) switch regions, which contain 5′-AGCT-3′ repeats in their core. How AID is recruited to switch regions remains unclear. Here we show that 14-3-3 adaptor proteins have an important role in CSR. 14-3-3 proteins specifically bound 5′-AGCT-3′ repeats, were upregulated in B cells undergoing CSR and were recruited with AID to the switch regions that are involved in CSR events (Sμ→Sγ1, Sμ→Sγ3 or Sμ→Sα). Moreover, blocking 14-3-3 by difopein, 14-3-3γ deficiency or expression of a dominant-negative 14-3-3σ mutant impaired recruitment of AID to switch regions and decreased CSR. Finally, 14-3-3 proteins interacted directly with AID and enhanced AID-mediated in vitro DNA deamination, further emphasizing the important role of these adaptors in CSR.

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Figure 1: 14-3-3 proteins bind 5′-AGCT-3′ repeats.
Figure 2: 14-3-3 adaptors bind to the switch regions involved in ongoing CSR.
Figure 3: 14-3-3 proteins are upregulated in germinal center B cells and in B cells undergoing CSR in vitro.
Figure 4: Blocking 14-3-3 by difopein inhibits 14-3-3 binding to 5′-AGCT-3′ repeats and hampers the binding of 14-3-3 and AID to switch regions.
Figure 5: Blocking 14-3-3 by difopein inhibits CSR in human and mouse B cells.
Figure 6: 14-3-3γ deficiency impaired CSR in mouse primary B cells.
Figure 7: 14-3-3σ Er dominant-negative mutant impaired CSR in mouse primary B cells.
Figure 8: 14-3-3 adaptors interact directly with AID.
Figure 9: 14-3-3 adaptors enhance AID-mediated DNA deamination.

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References

  1. Maizels, N. Immunoglobulin gene diversification. Annu. Rev. Genet. 39, 23–46 (2005).

    Article  CAS  Google Scholar 

  2. Casali, P. Somatic recombination and hypermutation in the immune system. in Lewin's Genes X (eds. Krebs, J.E., Goldstein, E.S. & Kilpatrick S.T.) 570–623 (Jones & Bartlett, Sudbury, Massachusetts, USA, 2009).

  3. Odegard, V.H. & Schatz, D.G. Targeting of somatic hypermutation. Nat. Rev. Immunol. 6, 573–583 (2006).

    Article  CAS  Google Scholar 

  4. Casali, P., Pal, Z., Xu, Z. & Zan, H. DNA repair in antibody somatic hypermutation. Trends Immunol. 27, 313–321 (2006).

    Article  CAS  Google Scholar 

  5. Teng, G. & Papavasiliou, F.N. Immunoglobulin somatic hypermutation. Annu. Rev. Genet. 41, 107–120 (2007).

    Article  CAS  Google Scholar 

  6. Peled, J.U. et al. The biochemistry of somatic hypermutation. Annu. Rev. Immunol. 26, 481–511 (2008).

    Article  CAS  Google Scholar 

  7. Stavnezer, J., Guikema, J.E. & Schrader, C.E. Mechanism and regulation of class switch recombination. Annu. Rev. Immunol. 26, 261–292 (2008).

    Article  CAS  Google Scholar 

  8. Xu, W. et al. Viral double-stranded RNA triggers Ig class switching by activating upper respiratory mucosa B cells through an innate TLR3 pathway involving BAFF. J. Immunol. 181, 276–287 (2008).

    Article  CAS  Google Scholar 

  9. Pone, E.J. et al. Toll-like receptors and B-cell receptors synergize to induce immunoglobulin class-switch DNA recombination: relevance to microbial antibody responses. Crit. Rev. Immunol. 30, 1–29 (2010).

    Article  CAS  Google Scholar 

  10. Muramatsu, M., Nagaoka, H., Shinkura, R., Begum, N.A. & Honjo, T. Discovery of activation-induced cytidine deaminase, the engraver of antibody memory. Adv. Immunol. 94, 1–36 (2007).

    Article  CAS  Google Scholar 

  11. Delker, R.K., Fugmann, S.D. & Papavasiliou, F.N. A coming-of-age story: activation-induced cytidine deaminase turns 10. Nat. Immunol. 10, 1147–1153 (2009).

    Article  CAS  Google Scholar 

  12. Park, S.R. et al. HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation. Nat. Immunol. 10, 540–550 (2009).

    Article  CAS  Google Scholar 

  13. Conticello, S.G., Langlois, M.A. & Neuberger, M.S. Insights into DNA deaminases. Nat. Struct. Mol. Biol. 14, 7–9 (2007).

    Article  CAS  Google Scholar 

  14. Chelico, L., Pham, P., Calabrese, P. & Goodman, M.F. APOBEC3G DNA deaminase acts processively 3′ → 5′ on single-stranded DNA. Nat. Struct. Mol. Biol. 13, 392–399 (2006).

    Article  CAS  Google Scholar 

  15. Nowarski, R., Britan-Rosich, E., Shiloach, T. & Kotler, M. Hypermutation by intersegmental transfer of APOBEC3G cytidine deaminase. Nat. Struct. Mol. Biol. 15, 1059–1066 (2008).

    Article  CAS  Google Scholar 

  16. Pham, P., Bransteitter, R., Petruska, J. & Goodman, M.F. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424, 103–107 (2003).

    Article  CAS  Google Scholar 

  17. Larijani, M. et al. AID associates with single-stranded DNA with high affinity and a long complex half-life in a sequence-independent manner. Mol. Cell. Biol. 27, 20–30 (2007).

    Article  CAS  Google Scholar 

  18. Chaudhuri, J., Khuong, C. & Alt, F.W. Replication protein A interacts with AID to promote deamination of somatic hypermutation targets. Nature 430, 992–998 (2004).

    Article  CAS  Google Scholar 

  19. Xu, Z. et al. Regulation of aicda expression and AID activity: relevance to somatic hypermutation and class switch DNA recombination. Crit. Rev. Immunol. 27, 367–397 (2007).

    Article  CAS  Google Scholar 

  20. Crouch, E.E. et al. Regulation of AID expression in the immune response. J. Exp. Med. 204, 1145–1156 (2007).

    Article  CAS  Google Scholar 

  21. Zan, H. et al. Lupus-prone MRL/Faslpr/lpr mice display increased AID expression and extensive DNA lesions, comprising deletions and insertions, in the immunoglobulin locus: concurrent upregulation of somatic hypermutation and class switch DNA recombination. Autoimmunity 42, 89–103 (2009).

    Article  CAS  Google Scholar 

  22. Aoufouchi, S. et al. Proteasomal degradation restricts the nuclear lifespan of AID. J. Exp. Med. 205, 1357–1368 (2008).

    Article  CAS  Google Scholar 

  23. Geisberger, R., Rada, C. & Neuberger, M.S. The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence. Proc. Natl. Acad. Sci. USA 106, 6736–6741 (2009).

    Article  CAS  Google Scholar 

  24. Ito, S. et al. Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1. Proc. Natl. Acad. Sci. USA 101, 1975–1980 (2004).

    Article  CAS  Google Scholar 

  25. McBride, K.M., Barreto, V., Ramiro, A.R., Stavropoulos, P. & Nussenzweig, M.C. Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase. J. Exp. Med. 199, 1235–1244 (2004).

    Article  CAS  Google Scholar 

  26. Patenaude, A.M. et al. Active nuclear import and cytoplasmic retention of activation-induced deaminase. Nat. Struct. Mol. Biol. 16, 517–527 (2009).

    Article  CAS  Google Scholar 

  27. Wang, M., Yang, Z., Rada, C. & Neuberger, M.S. AID upmutants isolated using a high-throughput screen highlight the immunity/cancer balance limiting DNA deaminase activity. Nat. Struct. Mol. Biol. 16, 769–776 (2009).

    Article  CAS  Google Scholar 

  28. Schrader, C.E., Linehan, E.K., Mochegova, S.N., Woodland, R.T. & Stavnezer, J. Inducible DNA breaks in Ig S regions are dependent on AID and UNG. J. Exp. Med. 202, 561–568 (2005).

    Article  CAS  Google Scholar 

  29. Zan, H. & Casali, P. AID- and Ung-dependent generation of staggered double-strand DNA breaks in immunoglobulin class switch DNA recombination: a post-cleavage role for AID. Mol. Immunol. 46, 45–61 (2008).

    Article  CAS  Google Scholar 

  30. Rada, C., Di Noia, J.M. & Neuberger, M.S. Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol. Cell 16, 163–171 (2004).

    Article  CAS  Google Scholar 

  31. Larson, E.D., Cummings, W.J., Bednarski, D.W. & Maizels, N. MRE11/RAD50 cleaves DNA in the AID/UNG-dependent pathway of immunoglobulin gene diversification. Mol. Cell 20, 367–375 (2005).

    Article  CAS  Google Scholar 

  32. Yan, C.T. et al. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature 449, 478–482 (2007).

    Article  CAS  Google Scholar 

  33. Dinkelmann, M. et al. Multiple functions of MRN in end-joining pathways during isotype class switching. Nat. Struct. Mol. Biol. 16, 808–813 (2009).

    Article  CAS  Google Scholar 

  34. Dunnick, W., Hertz, G.Z., Scappino, L. & Gritzmacher, C. DNA sequences at immunoglobulin switch region recombination sites. Nucleic Acids Res. 21, 365–372 (1993).

    Article  CAS  Google Scholar 

  35. Ehrenstein, M.R. & Neuberger, M.S. Deficiency in Msh2 affects the efficiency and local sequence specificity of immunoglobulin class-switch recombination: parallels with somatic hypermutation. EMBO J. 18, 3484–3490 (1999).

    Article  CAS  Google Scholar 

  36. Wu, X. et al. A role for the MutL mismatch repair Mlh3 protein in immunoglobulin class switch DNA recombination and somatic hypermutation. J. Immunol. 176, 5426–5437 (2006).

    Article  CAS  Google Scholar 

  37. Zarrin, A.A. et al. An evolutionarily conserved target motif for immunoglobulin class-switch recombination. Nat. Immunol. 5, 1275–1281 (2004).

    Article  CAS  Google Scholar 

  38. Luby, T.M., Schrader, C.E., Stavnezer, J. & Selsing, E. The μ switch region tandem repeats are important, but not required, for antibody class switch recombination. J. Exp. Med. 193, 159–168 (2001).

    Article  CAS  Google Scholar 

  39. Zarrin, A.A., Goff, P.H., Senger, K. & Alt, F.W.S. Sγ3 switch sequences function in place of endogenous Sγ1 to mediate antibody class switching. J. Exp. Med. 205, 1567–1572 (2008).

    Article  CAS  Google Scholar 

  40. Fu, H., Subramanian, R.R. & Masters, S.C. 14–3-3 proteins: structure, function, and regulation. Annu. Rev. Pharmacol. Toxicol. 40, 617–647 (2000).

    Article  CAS  Google Scholar 

  41. Morrison, D.K. The 14–3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol. 19, 16–23 (2009).

    Article  CAS  Google Scholar 

  42. Steinacker, P. et al. Unchanged survival rates of 14–3-3γ knockout mice after inoculation with pathological prion protein. Mol. Cell. Biol. 25, 1339–1346 (2005).

    Article  CAS  Google Scholar 

  43. Chan, T.A., Hermeking, H., Lengauer, C., Kinzler, K.W. & Vogelstein, B. 14-3-3σ is required to prevent mitotic catastrophe after DNA damage. Nature 401, 616–620 (1999).

    Article  CAS  Google Scholar 

  44. Zan, H. et al. The translesion DNA polymerase ζ plays a major role in Ig and bcl-6 somatic hypermutation. Immunity 14, 643–653 (2001).

    Article  CAS  Google Scholar 

  45. Wang, H., Zhang, L., Liddington, R. & Fu, H. Mutations in the hydrophobic surface of an amphipathic groove of 14-3-3ζ disrupt its interaction with Raf-1 kinase. J. Biol. Chem. 273, 16297–16304 (1998).

    Article  CAS  Google Scholar 

  46. Zannis-Hadjopoulos, M., Yahyaoui, W. & Callejo, M. 14-3-3 cruciform-binding proteins as regulators of eukaryotic DNA replication. Trends Biochem. Sci. 33, 44–50 (2008).

    Article  CAS  Google Scholar 

  47. Nakamura, M. et al. High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells. Int. Immunol. 8, 193–201 (1996).

    Article  CAS  Google Scholar 

  48. Aitken, A. et al. Specificity of 14-3-3 isoform dimer interactions and phosphorylation. Biochem. Soc. Trans. 30, 351–360 (2002).

    Article  CAS  Google Scholar 

  49. Hu, C.D., Chinenov, Y. & Kerppola, T.K. Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol. Cell 9, 789–798 (2002).

    Article  CAS  Google Scholar 

  50. Nagai, T. et al. A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat. Biotechnol. 20, 87–90 (2002).

    Article  CAS  Google Scholar 

  51. Barreto, V., Reina-San-Martin, B., Ramiro, A.R., McBride, K.M. & Nussenzweig, M.C. C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion. Mol. Cell 12, 501–508 (2003).

    Article  CAS  Google Scholar 

  52. Vuong, B.Q. et al. Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination. Nat. Immunol. 10, 420–426 (2009).

    Article  CAS  Google Scholar 

  53. Wang, L., Wuerffel, R., Feldman, S., Khamlichi, A.A. & Kenter, A.L. S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination. J. Exp. Med. 206, 1817–1830 (2009).

    Article  CAS  Google Scholar 

  54. Chang, B. & Casali, P. The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement. Trends Immunol. 15, 367–373 (1994).

    Article  CAS  Google Scholar 

  55. Pascual, D.W., Coste, M., Boyaka, P.N., Kiyono, H. & McGhee, J.R. Spontaneously hypertensive rat: cholera toxin converts suppression to immunity through a Th2 cell-IL-4 pathway. Am. J. Physiol. 273, R1509–R1518 (1997).

    Article  CAS  Google Scholar 

  56. Cunningham-Rundles, C. Physiology of IgA and IgA deficiency. J. Clin. Immunol. 21, 303–309 (2001).

    Article  CAS  Google Scholar 

  57. Wagner, B. IgE in horses: occurrence in health and disease. Vet. Immunol. Immunopathol. 132, 21–30 (2009).

    Article  CAS  Google Scholar 

  58. Ordinario, E.C., Yabuki, M., Larson, R.P. & Maizels, N. Temporal regulation of Ig gene diversification revealed by single-cell imaging. J. Immunol. 183, 4545–4553 (2009).

    Article  CAS  Google Scholar 

  59. Yaffe, M.B. et al. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91, 961–971 (1997).

    Article  CAS  Google Scholar 

  60. Diviani, D., Abuin, L., Cotecchia, S. & Pansier, L. Anchoring of both PKA and 14–3-3 inhibits the Rho-GEF activity of the AKAP-Lbc signaling complex. EMBO J. 23, 2811–2820 (2004).

    Article  CAS  Google Scholar 

  61. Mohammad, D.H. & Yaffe, M.B. 14-3-3 proteins, FHA domains and BRCT domains in the DNA damage response. DNA Repair (Amst.) 8, 1009–1017 (2009).

    Article  CAS  Google Scholar 

  62. Pasqualucci, L. et al. AID is required for germinal center-derived lymphomagenesis. Nat. Genet. 40, 108–112 (2008).

    Article  CAS  Google Scholar 

  63. Okazaki, I.M., Kotani, A. & Honjo, T. Role of AID in tumorigenesis. Adv. Immunol. 94, 245–273 (2007).

    Article  CAS  Google Scholar 

  64. Liu, M. & Schatz, D.G. Balancing AID and DNA repair during somatic hypermutation. Trends Immunol. 30, 173–181 (2009).

    Article  Google Scholar 

  65. Schaffer, A. et al. Selective inhibition of class switching to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements. J. Biol. Chem. 278, 23141–23150 (2003).

    Article  CAS  Google Scholar 

  66. Kim, E.C., Edmonston, C.R., Wu, X., Schaffer, A. & Casali, P. The HoxC4 homeodomain protein mediates activation of the immunoglobulin heavy chain 3′ hs1,2 enhancer in human B cells. Relevance to class switch DNA recombination. J. Biol. Chem. 279, 42258–42269 (2004).

    Article  CAS  Google Scholar 

  67. Lu, B., Xu, T., Park, S.K. & Yates, J.R. III. Shotgun protein identification and quantification by mass spectrometry. Methods Mol. Biol. 564, 261–288 (2009).

    Article  CAS  Google Scholar 

  68. Zan, H. et al. The translesion DNA polymerase θ plays a dominant role in immunoglobulin gene somatic hypermutation. EMBO J. 24, 3757–3769 (2005).

    Article  CAS  Google Scholar 

  69. Lois, C., Hong, E.J., Pease, S., Brown, E.J. & Baltimore, D. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295, 868–872 (2002).

    Article  CAS  Google Scholar 

  70. Zan, H., Wu, X., Komori, A., Holloman, W.K. & Casali, P. AID-dependent generation of resected double-strand DNA breaks and recruitment of Rad52/Rad51 in somatic hypermutation. Immunity 18, 727–738 (2003).

    Article  CAS  Google Scholar 

  71. Herron, B.J. et al. A mutation in stratifin is responsible for the repeated epilation (Er) phenotype in mice. Nat. Genet. 37, 1210–1212 (2005).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. Muslin (Washington University) and A. Wynshaw-Boris (Univ. of California, San Francisco) for advice, I. McLeod for performing MudPIT, H. Hermeking and D. Lodygin (Ludwig-Maximilians-Univ.) for sharing preliminary data on 14-3-3σ, J.S. Hawkins and M. Crabtree for transcripts analysis, P. Patel, A. Bui and S. Yao for technical assistance, L. Yang and D. Baltimore (Caltech) for the pFUW lentiviral constructs, C. Murre (Univ. of California, San Diego) for the pTAC retroviral construct, F. Byrne and R. Kurzeja (Amgen) for the purified recombinant AID, Y. Du for the purified recombinant 14-3-3 proteins and the University of California, Irvine Pathology Research Core Facility for immunohistochemistry. S.-R.P. was a fellow of the Korea Research Foundation. H.F. is a Georgia Cancer Coalition Distinguished Cancer Scholar and a Georgia Research Alliance Distinguished Investigator. P.C. is the Donald L. Bren Professor of Medicine, Molecular Biology and Biochemistry. H.F. was supported by US National Institutes of Health (NIH) grant P01 CA 116676. J.R.Y. III was supported by NIH grant P41 RR011823. This work was supported by NIH grants AI 045011, AI 079705 and AI 060573 to P.C.

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  1. Zsolt Fulop & Seok-Rae Park

    Present address: Present addresses: Department of Gastroenterology, St. John's Hospital and United Hospitals of Northern Buda of the Metropolitan Government, Budapest, Hungary (Z.F.); Department of Microbiology, College of Medicine, Konyang University, Daejeon, Republic of Korea (S.-R.P.).,

Authors and Affiliations

  1. Institute for Immunology, School of Medicine and School of Biological Sciences, University of California, Irvine, California, USA

    Zhenming Xu, Zsolt Fulop, Egest J Pone, Jinsong Zhang, Thach Mai, Lisa M Thomas, Ahmed Al-Qahtani, Clayton A White, Seok-Rae Park, Hong Zan & Paolo Casali

  2. Department of Biological Chemistry, School of Medicine, University of California, Irvine, California, USA

    Guikai Wu

  3. Department of Neurology, University of Ulm, Ulm, Germany

    Petra Steinacker & Markus Otto

  4. Department of Pharmacology, School of Medicine, Emory University, Atlanta, Georgia, USA

    Zenggang Li & Haian Fu

  5. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA

    John Yates III

  6. New York State Department of Health, Wadsworth Center, Albany, New York, USA

    Bruce Herron

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Contributions

Z.X., Z.F., G.W., E.J.P., J.Z., T.M., L.M.T., A.A.-Q., C.A.W., S.-R.P., Z.L. and H.Z. performed experimental work; J.R.Y. III was responsible for the MudPIT analysis; B.H. provided 14-3-3σ+/Er mice; P.S. and M.O. provided 14-3-3γ−/− mice; H.F. provided recombinant 14-3-3 proteins, 14-3-3 isoform-specific antibodies and the difopein-expressing construct; H.Z. designed experiments; Z.X. designed experiments and prepared the manuscript; P.C. designed experiments, supervised the project and prepared the manuscript.

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Correspondence to Paolo Casali.

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Xu, Z., Fulop, Z., Wu, G. et al. 14-3-3 adaptor proteins recruit AID to 5′-AGCT-3′–rich switch regions for class switch recombination. Nat Struct Mol Biol 17, 1124–1135 (2010). https://doi.org/10.1038/nsmb.1884

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