REVIEW PAPER
Activation-induced cytidine deaminase (AID): single activity – pleiotropic effect
 
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Publication date: 2014-10-23
 
 
BioTechnologia 2013;94(1):15-21
 
ABSTRACT
Activation-induced cytidine deaminase (AID) plays an essential role in the generation of a highly competent repertoire
of antibodies by participating in class switch recombination (CSR) and somatic hypermutation (SHM). After
B cell stimulation by antigens, AID initiates SHM and CSR by deamination of cytidine to uridine in the variable
and constant regions of Ig genes. An adverse effect of AID’s ability to directly modify genome sequences is its
mutagenic potential. AID has been shown to occasionally target non-Ig genes and its abnormal expression is
strongly associated with tumorigenesis. Aberrant AID expression can also be triggered by some oncogenic pathogens,
such as Helicobacter pylori and several viruses. The latest reports show that also under physiological conditions
AID might act beyond the immune system. Data exist suggesting that AID can play a role in the process
of active genome demethylation – the heart of epigenetic gene activation and reprogramming. Moreover, it has
been shown that abnormal genome demethylation mediated by AID might be associated with human colon cancers.
The potential role of AID in the active demethylation process is still controversial, but the hypothesis that
aberrant AID expression may cause cancerogenesis by changing genome methylation patterns appears highly
attractive. As a unique human enzyme able to induce both genetic and epigenetic alterations under physiological
and pathological conditions, AID could be a promising and versatile drug target. In this review we present the
current state of knowledge on this topic and the controversies surrounding the pleiotropic effect of AID function.
REFERENCES (43)
1.

Albesiano E., Messmer B.T., Damle R.N., Allen S.L., Rai K.R., Chiorazzi N. (2003) Blood 102: 3333-3339.
 
2.

Arakawa H., Saribasak H., Buerstedde J.M. (2004) PLoS Biol. 2: E179. Basu U., Meng F.L., Keim C., Grinstein V., Pefanis E., Eccleston J., Zhang T., Myers D., Wasserman C.R.,
Wesemann D.R. et al. (2011) Cell 144: 353-363.
 
3.

Basu U., Wang Y., Alt F.W. (2008) Mol. Cell 32: 285-291.
 
4.

Bestor T.H. (2000) Hum. Mol. Genet. 9: 2395-2402. Bhutani N., Brady J.J., Damian M., Sacco A., Corbel S.Y.,.
 
5.

Blau H.M. (2010) Nature 463: 1042-1047.
 
6.

Bransteitter R., Pham P., Scharff M.D., Goodman M.F. (2003) Proc. Natl Acad. Sci. USA 100: 4102-4107.
 
7.

Bransteitter R., Prochnow C., Chen X.S. (2009) Cell Mol. Life Sci. 66: 3137-3147.
 
8.

Brar S.S., Sacho E.J., Tessmer I., Croteau D.L., Erie D.A., Diaz M. (2008) DNA Repair (Amst) 7: 77-87.
 
9.

Chatterji M., Unniraman S., McBride K.M., Schatz D.G. (2007) J. Immunol. 179: 5274-5280. Chaudhuri J., Alt F.W. (2004) Nat. Rev. Immunol. 4: 541-552.
 
10.

Chaudhuri J., Tian M., Khuong C.,.
 
11.

Chua K., Pinaud E., Alt F.W. (2003) Nature 422: 726-730. Cheng H.L., Vuong B.Q., Basu U., Franklin A., Schwer B., Astarita J., Phan R.T., Datta A., Manis J., Alt F.W. et al. (2009) Proc. Natl Acad. Sci. USA 106: 2717-2722. Chiba T., Marusawa H. (2009) J. Mol. Med. 87: 1023-1027.
 
12.

Conticello S.G. (2008) Genome Biol. 9: 229. Crouch E.E., Li Z., Takizawa M., Fichtner-Feigl S., Gourzi P., Montano C., Feigenbaum L., Wilson P., Janz S., Papavasiliou F.N. et al. (2007) J. Exp. Med. 204: 1145-1156.
 
13.

de Yebenes V.G., Ramiro A.R. (2006) Trends Mol. Med. 12: 432-439.
 
14.

Delker R.K., Fugmann S.D., Papavasiliou F.N. (2009) Nat. Immunol. 10: 1147-1153.
Durandy A., Peron S., Taubenheim N., Fischer A. (2006) Hum. Mutat. 27: 1185-1191.
Gehring M., Reik W., Henikoff S. (2009) Trends Genet. 25: 82-90.
 
15.

Hajkova P., Erhardt S., Lane N., Haaf T., El-Maarri O., Reik W., Walter J., Surani M.A. (2002) Mech. Dev. 117: 15-23.
 
16.

Holden L.G., Prochnow C., Chang Y.P., Bransteitter R., Chelico L., Sen U., Stevens R.C.,
Goodman M.F., Chen X.S. (2008) Nature 456: 121-124.
 
17.
Holmes R.K., Malim M.H., Bishop K.N. (2007) Trends Biochem. Sci. 32: 118-128.
Illingworth R.S., Bird A.P. (2009) FEBS Lett. 583: 1713-1720.
 
18.

Kim C.J., Song J.H., Cho Y.G., Cao Z., Kim S.Y., Nam S.W., Lee J.Y., Park W.S. (2007) Tumour Biol. 28: 333-339.
 
19.

Kinoshita K., Nonaka T. (2006) Int. J. Hematol. 83: 201-207. Kou T., Marusawa H.,
Kinoshita K., Endo Y., Okazaki I.M., Ueda Y., Kodama Y., Haga H., Ikai I., Chiba T. (2007) Int. J. Cancer 120: 469-476.
 
20.

Kuppers R. (2005) Nat. Rev. Cancer 5: 251-262.
 
21.
Liao W., Hong S.H., Chan B.H., Rudolph F.B., Clark S.C., Chan L. (1999) Biochem. Biophys. Res. Commun. 260: 398-404.
 
22.
Losey H.C., Ruthenburg A.J., Verdine G.L. (2006) Nat. Struct. Mol. Biol. 13: 153-159.
MacDuff D.A., Neuberger M.S., Harris R.S. (2006) Mol. Immunol. 43: 1099-1108.
Mantovani A., Allavena P., Sica A., Balkwill F. (2008) Nature 454: 436-444.
 
23.

Morgan H.D., Dean W., Coker H.A., Reik W., Petersen-Mahrt S.K. (2004) J. Biol. Chem. 279: 52353-52360.
 
24.

Morisawa T.,.
 
25.

Marusawa H., Ueda Y., Iwai A., Okazaki I.M., Honjo T., Chiba T. (2008) Int. J. Cancer 123: 2735-2740.
 
26.

Muramatsu M., Kinoshita K., Fagarasan S., Yamada S., Shinkai Y., Honjo T. (2000) Cell 102: 553-563. Muramatsu M., Sankaranand V.S., Anant S., Sugai M., Kinoshita K., Davidson
N.O., Honjo T. (1999) J. Biol. Chem. 274: 18470-18476.
 
27.
Okazaki I.M., Hiai H., Kakazu N., Yamada S., Muramatsu M., Kinoshita K., Honjo T. (2003) J. Exp. Med. 197: 1173-1181.
 
28.

Oscier D.G., Gardiner A.C., Mould S.J., Glide S., Davis Z.A., Ibbotson R.E., Corcoran M.M., Chapman R.M., Thomas P.W., Copplestone J.A. et al. (2002) Blood 100: 1177- 1184. Pavri R., Gazumyan A., Jankovic M., Di Virgilio M., Klein I., Ansarah-Sobrinho C., Resch W., Yamane A., Reina SanMartin B., Barreto V. et al. (2010) Cell 143: 122-133.
 
29.

Peled J.U., Kuang F.L., Iglesias-Ussel M.D., Roa S., Kalis S.L., Goodman M.F., Scharff M.D. (2008) Annu. Rev. Immunol. 26: 481-511.
 
30.
v Petersen-Mahrt S.K., Harris R.S., Neuberger M.S. (2002) Nature 418: 99-103. Popp C., Dean W., Feng S., Cokus S.J., Andrews S., Pellegrini M., Jacobsen S.E., Reik W. (2010) Nature 463: 1101-1105.
 
31.

Prochnow C., Bransteitter R., Chen X.S. (2009) Sci. China C: Life Sci. 52: 893-902.
Prochnow C., Bransteitter R., Klein M.G., Goodman M.F., Chen X.S. (2007) Nature 445: 447-451. Rai K., Huggins I.J., James S.R., Karpf A.R., Jones D.A., Cairns B.R. (2008) Cell 135: 1201-1212.
 
32.

Rai K., Sarkar S., Broadbent T.J., Voas M., Grossmann K.F., Nadauld L.D., Dehghanizadeh S., Hagos F.T., Li Y., Toth R.K. et al. (2010) Cell 142: 930-942.
 
33.

Ramiro A.R., Jankovic M., Eisenreich T., Difilippantonio S., Chen-Kiang S., Muramatsu M., Honjo T., Nussenzweig A., Nussenzweig M.C. (2004) Cell 118: 431-438.
 
34.

Revy P., Muto T., Levy Y., Geissmann F., Plebani A., Sanal O., Catalan N., Forveille M., Dufourcq-Labelouse R., Gennery A. et al. (2000) Cell 102: 565-575.
 
35.

Rogozin I.B., Basu M.K., Jordan I.K., Pavlov Y.I., Koonin E.V. (2005) Cell Cycle 4: 1281-1285.
 
36.

Rogozin I.B., Iyer L.M., Liang L., Glazko G.V., Liston V.G., Pavlov Y.I., Aravind L., Pancer Z. (2007) Nat. Immunol. 8: 647-656.
 
37.

Samaranayake M., Bujnicki J.M., Carpenter M., Bhagwat A.S. (2006)DNA Repair. Chem. Rev. 106: 700-719.
 
38.

Shen H.M., Storb U. (2004) Proc. Natl Acad. Sci. USA 101: 12997-13002.
 
39.

Shinkura R., Ito S., Begum N.A., Nagaoka H., Muramatsu M., Kinoshita K., Sakakibara Y., Hijikata H., Honjo T. (2004) Nat. Immunol. 5: 707-712.
 
40.

Smith H.C., Bennett R.P., Kizilyer A., McDougall W.M., Prohaska K.M. (2011) Semin. Cell Dev. Biol. 23: 258-268.
 
41.

Stavnezer J. (2011) Trends Immunol. 32: 194-201. Teng B., Burant C.F., Davidson N.O. (1993) Science 260: 1816-1819. Unniraman S.,.
 
42.

Schatz D.G. (2007) Science 317: 1227-1230. Yamane A., Resch W., Kuo N., Kuchen S., Li
Z., Sun H.W., Robbiani D.F., McBride K., Nussenzweig M.C., Casellas R. (2011) Nat. Immunol. 12: 62-69.
 
43.

Zarrin A.A., Alt F.W., Chaudhuri J., Stokes N., Kaushal D., Du Pasquier L., Tian M. (2004) Nat. Immunol. 5: 1275-1281.
 
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