Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1

被引:239
作者
Ito, S [1 ]
Nagaoka, H [1 ]
Shinkura, R [1 ]
Begum, N [1 ]
Muramatsu, M [1 ]
Nakata, M [1 ]
Honjo, T [1 ]
机构
[1] Kyoto Univ, Dept Med Chem, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan
关键词
D O I
10.1073/pnas.0307335101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Activation-induced cytidine deaminase (AID) is a molecule central to initiating class switch recombination, somatic hypermutation, and gene conversion of Ig genes. However, its mechanism to initiate these genetic alterations is still unclear. AID can convert cytosine to uracil on either mRNA or DNA and is involved in DNA cleavage. Although these events are expected to take place in the nucleus, overexpressed AID was found predominantly in the cytoplasm. Here, we demonstrated that AID is a nucleocytoplasmic shuttling protein with a bipartite nuclear localization signal and a nuclear export signal in its N and C termini, respectively. In addition to previously identified genetic, structural, and biochemical similarities of AID with apolipoprotein B mRNA editing catalytic polypeptide 1, an RNA editing enzyme of ApoB100 mRNA, the present finding provides another aspect to their resemblance, suggesting that both may have homologous reaction mechanisms.
引用
收藏
页码:1975 / 1980
页数:6
相关论文
共 37 条
[1]   Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion [J].
Arakawa, H ;
Hauschild, J ;
Buerstedde, JM .
SCIENCE, 2002, 295 (5558) :1301-1306
[2]   C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion [J].
Barreto, V ;
Reina-San-Martin, B ;
Ramiro, AR ;
McBride, KM ;
Nussenzweig, MC .
MOLECULAR CELL, 2003, 12 (02) :501-508
[3]  
Bogerd HP, 1996, MOL CELL BIOL, V16, P4207
[4]   Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase [J].
Bransteitter, R ;
Pham, P ;
Scharff, MD ;
Goodman, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :4102-4107
[5]   Transcription-targeted DNA deamination by the AID antibody diversification enzyme [J].
Chaudhuri, J ;
Tian, M ;
Khuong, C ;
Chua, K ;
Pinaud, E ;
Alt, FW .
NATURE, 2003, 422 (6933) :726-730
[6]   The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decay [J].
Chester, A ;
Somasekaram, A ;
Tzimina, M ;
Jarmuz, A ;
Gisbourne, J ;
O'Keefe, R ;
Scott, J ;
Navaratnam, N .
EMBO JOURNAL, 2003, 22 (15) :3971-3982
[7]   Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase [J].
Di Noia, J ;
Neuberger, MS .
NATURE, 2002, 419 (6902) :43-48
[8]   AID mediates hypermutation by deaminating single stranded DNA [J].
Dickerson, SK ;
Market, E ;
Besmer, E ;
Papavasiliou, EN .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (10) :1291-1296
[9]   De novo protein synthesis is required for the activation-induced cytidine deaminase function in class-switch recombination [J].
Doi, T ;
Kinoshita, K ;
Ikegawa, M ;
Muramatsu, M ;
Honjo, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2634-2638
[10]   RNA-editing cytidine deaminase Apobec-1 is unable to induce somatic hypermutation in mammalian cells [J].
Eto, T ;
Kinoshita, K ;
Yoshikawa, K ;
Muramatsu, M ;
Honjo, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (22) :12895-12898