Nuclear interaction of the dynein light chain LC8a with the TRPS1 transcription factor suppresses the transcriptional repression activity of TRPS1

被引:58
作者
Kaiser, FJ
Tavassoli, K
Van den Bemd, GJ
Chang, GTG
Horsthemke, B
Möröy, T
Lüdecke, HJ
机构
[1] Univ Klinikum, Inst Human Genet, D-45122 Essen, Germany
[2] Univ Klinikum, Inst Zellbiol, D-45122 Essen, Germany
[3] Erasmus Med Ctr, Dept Reprod & Dev, NL-3000 DR Rotterdam, Netherlands
关键词
D O I
10.1093/hmg/ddg145
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
The TRPS1 gene codes for a 1281 amino acids nuclear transcription factor with an unusual combination of different types of zinc finger motifs, including GATA-type DNA-binding and IKAROS-like zinc fingers. TRPS1 is a repressor of GATA-regulated genes and implicated in the human tricho-rhino-phalangeal syndromes. We found that two distinct regions of TRPS1 can physically interact with the dynein light chain 8 protein, LC8a, that are at least 458 amino acids apart from each other. Region A covers 89 amino acids (635-723), spanning three potential C2H2 zinc finger structures, and region B covers the 100 most C-terminal amino acids (1182-1281) containing the IKAROS-like motif. LC8a is known to interact with more than 10 different molecules, both proteins and nucleic acids. In most cases, LC8a was identified as a transport molecule in the cytoplasm. Interestingly, we found that LC8a co-localizes with TRPS1 in dot-like structures in the cell nucleus. In an electrophoretic mobility shift assay we could show that the interaction of LC8a and TRPS1 lowers the binding of TRPS1 to the GATA consensus sequence. In addition, GATA-regulated reporter gene assay indicated that LC8a is able to suppress the transcriptional repression activity of TRPS1.
引用
收藏
页码:1349 / 1358
页数:10
相关论文
共 35 条
[1]   African swine fever virus protein p54 interacts with the microtubular motor complex through direct binding to light-chain dynein [J].
Alonso, C ;
Miskin, J ;
Hernáez, B ;
Fernandez-Zapatero, P ;
Soto, L ;
Cantó, C ;
Rodríguez-Crespo, I ;
Dixon, L ;
Escribano, JM .
JOURNAL OF VIROLOGY, 2001, 75 (20) :9819-9827
[2]   Bcl-2 lies downstream of parathyroid hormone-related peptide in a signaling pathway that regulates chondrocyte maturation during skeletal development [J].
Amling, M ;
Neff, L ;
Tanaka, S ;
Inoue, D ;
Kuida, K ;
Weir, E ;
Philbrick, WM ;
Broadus, AE ;
Baron, R .
JOURNAL OF CELL BIOLOGY, 1997, 136 (01) :205-213
[3]  
BARTEL P, 1993, BIOTECHNIQUES, V14, P920
[4]   Characterization of a zinc-finger protein and its association with apoptosis in prostate cancer cells [J].
Chang, GTG ;
Steenbeek, M ;
Schippers, E ;
Blok, LJ ;
van Weerden, WM ;
van Alewijk, DCJG ;
Eussen, BHJ ;
van Steenbrugge, GJ ;
Brinkmann, AO .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (17) :1414-1421
[5]   Structure and function of GC79/TRPS1, a novel androgen-repressible apoptosis gene [J].
Chang, GTG ;
van den Bemd, GJCM ;
Jhamai, M ;
Brinkmann, AO .
APOPTOSIS, 2002, 7 (01) :13-21
[6]   I kappa B alpha physically interacts with a cytoskeleton-associated protein through its signal response domain [J].
Crepieux, P ;
Kwon, H ;
Leclerc, N ;
Spencer, W ;
Richard, S ;
Lin, RT ;
Hiscott, J .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (12) :7375-7385
[7]  
Dick T, 1996, MOL CELL BIOL, V16, P1966
[8]   Dynein light chain binding to a 3′-untranslated sequence mediates parathyroid hormone mRNA association with microtubules [J].
Epstein, E ;
Sela-Brown, A ;
Ringel, I ;
Kilav, R ;
King, SM ;
Benashski, SE ;
Yisraeli, JK ;
Silver, J ;
Naveh-Many, T .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (04) :505-512
[9]  
Espindola FS, 2000, CELL MOTIL CYTOSKEL, V47, P269, DOI 10.1002/1097-0169(200012)47:4<269::AID-CM2>3.0.CO
[10]  
2-G