Regulation of poly(A) polymerase by 14-3-3ε

被引:17
作者
Kim, H
Lee, JH
Lee, Y [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Dept Chem, Taejon 305701, South Korea
[2] Korea Adv Inst Sci & Technol, Ctr Mol Design & Synth, Taejon 305701, South Korea
关键词
phosphorylation; poly(A) polymerase; polyadenylation activity; protein-protein interaction; 14-3-3; epsilon;
D O I
10.1093/emboj/cdg486
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
Poly(A) polymerase (PAP) is a key enzyme responsible for the addition of the poly(A) at the 3' end of pre-mRNA. The C-terminal region of mammalian PAP carries target sites for protein-protein interaction with the 25 kDa subunit of cleavage factor I and with splicing factors U1A and U2AF65. We used a yeast two-hybrid screen to identify 14-3-3epsilon as an additional protein binding to the C-terminal region of PAP. Interaction between PAP and 14-3-3epsilon was confirmed by both in vitro and in vivo binding assays. This interaction is dependent on PAP phosphorylation. Deletion analysis of PAP suggests that PAP contains multiple binding sites for 14-3-3epsilon. The binding of 14-3-3epsilon to PAP inhibits the polyadenylation activity of PAP in vitro, and overexpression of 14-3-3epsilon leads to a shorter poly(A) mRNA tail in vivo. In addition, the interaction between PAP and 14-3-3epsilon redistributes PAP within the cell by increasing its cytoplasmic localization. These data suggest that 14-3-3epsilon is involved in regulating both the activity and the nuclear/ cytoplasmic partitioning of PAP through the phosphorylation-dependent interaction.
引用
收藏
页码:5208 / 5219
页数:12
相关论文
共 50 条
[1]  
BALLANTYNE S, 1995, RNA, V1, P64
[2]   Last but not least: Regulated poly(A) tail formation [J].
Barabino, SML ;
Keller, W .
CELL, 1999, 99 (01) :9-11
[3]   DEGRADATION OF MESSENGER-RNA IN EUKARYOTES [J].
BEELMAN, CA ;
PARKER, R .
CELL, 1995, 81 (02) :179-183
[4]   14-3-3σ is required to prevent mitotic catastrophe after DNA damage [J].
Chan, TA ;
Hermeking, H ;
Lengauer, C ;
Kinzler, KW ;
Vogelstein, B .
NATURE, 1999, 401 (6753) :616-620
[5]   Cell-cycle related regulation poly(A) polymerase by phosphorylation [J].
Colgan, DF ;
Murthy, KGK ;
Prives, C ;
Manley, JL .
NATURE, 1996, 384 (6606) :282-285
[6]   Inhibition of poly(A) polymerase requires p34cdc2/cyclin B phosphorylation of multiple consensus and non-consensus sites [J].
Colgan, DF ;
Murthy, KG ;
Zhao, W ;
Prives, C ;
Manley, JL .
EMBO JOURNAL, 1998, 17 (04) :1053-1062
[7]  
Craparo A, 1997, J BIOL CHEM, V272, P11663
[8]   BINDING OF 14-3-3-PROTEINS TO THE PROTEIN-KINASE RAF AND EFFECTS ON ITS ACTIVATION [J].
FREED, E ;
SYMONS, M ;
MACDONALD, SG ;
MCCORMICK, F ;
RUGGIERI, R .
SCIENCE, 1994, 265 (5179) :1713-1716
[9]   Involvement of the carboxyl terminus of vertebrate poly(A) polymerase in U1A autoregulation and in the coupling of splicing and polyadenylation [J].
Gunderson, SI ;
Vagner, S ;
PolycarpouSchwarz, M ;
Mattaj, IW .
GENES & DEVELOPMENT, 1997, 11 (06) :761-773
[10]  
Huang YQ, 1996, MOL CELL BIOL, V16, P1534