Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions

被引:97
作者
Örd, D
Örd, T
机构
[1] Estonian Bioctr, EE-51010 Tartu, Estonia
[2] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia
关键词
NIPK; TRB3; gene expression; stress response; endoplasmic reticulum; arsenite; ATF4;
D O I
10.1016/j.bbrc.2005.02.149
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 neuronal cell death-inducible putative kinase (NIPK) gene is upregulated in several cell types under stressful conditions. In order to understand the molecular control of the human (h) NIPK gene (also known as TRB3 and SKIP3), we mapped the transcriptional start sites of the gene in HepG2 cells treated with thapsigargin, the inhibitor of endoplasmic reticular Ca2+-ATPase, and determined the promoter region of the gene which is essential for endoplasmic reticulum and arsenite stress responses. The analysis of cDNA clones revealed the presence of several hNIPK mRNA isoforms, differing in their 5' regions upstream of the hNIPK translation initiation codon as a result of alternative transcription initiation and alternative splicing. The induction of hNIPK gene in response to thapsigargin and arsenite treatments is mediated by a promoter segment consisting of tandemly arranged 33-bp repeats that contain a regulatory element similar to C/EBP-ATF composite site of the Chop gene promoter. ATF4, whose level is upregulated in the cells exposed to thapsigargin or arsenite, is able to bind to the 33-bp repeat and activate the hNIPK promoter. The coexpression of hNIPK inhibits activation of hNIPK promoter in response to the stress-inducing agents and to overexpressed ATF4, and thus NIPK may function as a negative feedback regulator of ATF4. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:210 / 218
页数:9
相关论文
共 23 条
[1]   Transcriptional and replicational activation functions in the bovine papillomavirus type 1 E2 protein are encoded by different structural determinants [J].
Abroi, A ;
Kurg, R ;
Ustav, M .
JOURNAL OF VIROLOGY, 1996, 70 (09) :6169-6179
[2]   Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation [J].
Averous, J ;
Bruhat, A ;
Jousse, C ;
Carraro, V ;
Thiel, G ;
Fafournoux, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (07) :5288-5297
[3]  
Barbosa-Tessmann IP, 2000, J BIOL CHEM, V275, P26976
[4]   SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia [J].
Bowers, AJ ;
Scully, S ;
Boylan, JF .
ONCOGENE, 2003, 22 (18) :2823-2835
[5]   Amino acids control mammalian gene transcription:: Activating transcription factor 2 is essential for the amino acid responsiveness of the CHOP promoter [J].
Bruhat, A ;
Jousse, C ;
Carraro, V ;
Reimold, AM ;
Ferrara, M ;
Fafournoux, P .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (19) :7192-7204
[6]   Differences in the molecular mechanisms involved in the transcriptional activation of the CHOP and asparagine synthetase genes in response to amino acid deprivation or activation of the unfolded protein response [J].
Bruhat, A ;
Averous, J ;
Carraro, V ;
Zhong, C ;
Reimold, AM ;
Kilberg, MS ;
Fafournoux, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (50) :48107-48114
[7]   TRB3:: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver [J].
Du, KY ;
Herzig, S ;
Kulkarni, RN ;
Montminy, M .
SCIENCE, 2003, 300 (5625) :1574-1577
[8]   Complexes containing activating transcription factor (ATF)/cAMP-responsive-element-binding protein (CREB) interact with the CCAAT enhancer-binding protein (C/EBP)-ATF composite site to regulate Gadd153 expression during the stress response [J].
Fawcett, TW ;
Martindale, JL ;
Guyton, KZ ;
Hai, T ;
Holbrook, NJ .
BIOCHEMICAL JOURNAL, 1999, 339 :135-141
[9]   PROTEIN KINASES .6. THE EUKARYOTIC PROTEIN-KINASE SUPERFAMILY - KINASE (CATALYTIC) DOMAIN-STRUCTURE AND CLASSIFICATION [J].
HANKS, SK ;
HUNTER, T .
FASEB JOURNAL, 1995, 9 (08) :576-596
[10]   Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein - Implication for heme oxygenase-1 gene regulation [J].
He, CH ;
Gong, PF ;
Hu, B ;
Stewart, D ;
Choi, ME ;
Choi, AMK ;
Alam, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (24) :20858-20865