AUF1 is a bcl-2 A+U-rich element-binding protein involved in bcl-2 mRNA destabilization during apoptosis

被引:81
作者
Lapucci, A
Donnini, M
Papucci, L
Witort, E
Tempestini, A
Bevilacqua, A
Nicolin, A
Brewer, G
Schiavone, N
Capaccioli, S
机构
[1] Univ Florence, Sch Med, Dept Expt Pathol & Oncol, I-50134 Florence, Italy
[2] Univ Milan, Sch Med, Dept Pharmacol, I-20129 Milan, Italy
[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA
关键词
D O I
10.1074/jbc.M201377200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously identified a conserved A + U-rich element (ARE) in the 3'-untranslated region of bcl-2 mRNA. We have also recently demonstrated that the bcl-2 ARE interacts with a number of ARE-binding proteins (AUBPs) whose pattern changes during apoptosis in association with bcl-2 mRNA half-life reduction. Here we show that the AUBP AUF1 binds in vitro to bcl-2 mRNA. The results obtained in a yeast RNA three-hybrid system have demonstrated that the 1-257-amino acid portion of p37 AUF1 (conserved in all isoforms), containing the two RNA recognition motifs, also binds to the bcl-2 ARE in vivo. UVC irradiation-induced apoptosis results in an increase of AUF1. Inhibition of apoptosis by a general caspase inhibitor reduces this increase by 2-3-fold. These results indicate involvement of AUF1 in the ARE/ AUBP-mediated modulation of bcl-2 mRNA decay during apoptosis.
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收藏
页码:16139 / 16146
页数:8
相关论文
共 45 条
[31]   Identification of AUF1 as a parathyroid hormone mRNA 3′-untranslated region-binding protein that determines parathyroid hormone mRNA stability [J].
Sela-Brown, A ;
Silver, J ;
Brewer, G ;
Naveh-Many, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (10) :7424-7429
[32]   ALTERNATIVE PROMOTERS AND EXONS, SOMATIC MUTATION AND DEREGULATION OF THE BCL-2-IG FUSION GENE IN LYMPHOMA [J].
SETO, M ;
JAEGER, U ;
HOCKETT, RD ;
GRANINGER, W ;
BENNETT, S ;
GOLDMAN, P ;
KORSMEYER, SJ .
EMBO JOURNAL, 1988, 7 (01) :123-131
[33]   A CONSERVED AU SEQUENCE FROM THE 3' UNTRANSLATED REGION OF GM-CSF MESSENGER-RNA MEDIATES SELECTIVE MESSENGER-RNA DEGRADATION [J].
SHAW, G ;
KAMEN, R .
CELL, 1986, 46 (05) :659-667
[34]   Testosterone and dihydrotestosterone regulate AUF1 isoforms in a tissue-specific fashion in the mouse [J].
Sheflin, LG ;
Spaulding, SW .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2000, 278 (01) :E50-E57
[35]  
Suzuki A, 1996, ONCOGENE, V13, P31
[36]   Bcl-2 family: Life-or-death switch [J].
Tsujimoto, Y ;
Shimizu, S .
FEBS LETTERS, 2000, 466 (01) :6-10
[37]   Structure and genomic organization of the human AUF1 gene: Alternative pre-mRNA splicing generates four protein isoforms [J].
Wagner, BJ ;
DeMaria, CT ;
Sun, Y ;
Wilson, GM ;
Brewer, G .
GENOMICS, 1998, 48 (02) :195-202
[38]   HuR regulates p21 mRNA stabilization by UV light [J].
Wang, WG ;
Furneaux, H ;
Cheng, HM ;
Caldwell, MC ;
Hutter, D ;
Liu, YS ;
Holbrook, N ;
Gorospe, M .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (03) :760-769
[39]   Assembly of AUF1 oligomers on U-rich RNA targets by sequential dimer association [J].
Wilson, GM ;
Sun, Y ;
Lu, HP ;
Brewer, G .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (47) :33374-33381
[40]   Identification and characterization of proteins binding A+U-rich elements [J].
Wilson, GM ;
Brewer, G .
METHODS, 1999, 17 (01) :74-83