IDENTIFICATION OF A NOVEL INTERLEUKIN-6 RESPONSE ELEMENT CONTAINING AN ETS-BINDING SITE AND A CRE-LIKE SITE IN THE JUNB PROMOTER

被引:130
作者
NAKAJIMA, K [1 ]
KUSAFUKA, T [1 ]
TAKEDA, T [1 ]
FUJITANI, Y [1 ]
NAKAE, K [1 ]
HIRANO, T [1 ]
机构
[1] OSAKA UNIV, SCH MED, BIOMED RES CTR, DIV MOLEC ONCOL, SUITA, OSAKA 565, JAPAN
关键词
D O I
10.1128/MCB.13.5.3027
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
Interleukin-6 (IL-6) activation of the immediate-early gene junB has been shown to require both a tyrosine kinase and an unknown 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7)-sensitive pathway. Here we report the identification and characterization of an IL-6 immediate-early response element in the junB promoter (designated JRE-IL6) in HepG2 cells. The JRE-IL6 element, located at -149 to -124, contains two DNA motifs, an Ets-binding site (EBS) (CAGGAAGC) and a CRE-like site (TGACGCGA). Functional studies using variously mutated JRE-IL6 elements showed that both motifs were necessary and sufficient for IL-6 response of the promoter. The EBS of the JRE-IL6 element (JEBS) appears to bind a protein in the Ets family or a related protein which could also form a major complex with the EBSs of the murine sarcoma virus long terminal repeat or human T-cell leukemia virus type 1 long terminal repeat. The CRE-like site appears to weakly bind multiple CREB-ATF family proteins. Despite the similarity in the structure between the JRE-IL6 element and the polyomavirus enhancer PyPEA3, composed of an EBS and an AP1-binding site and known to be activated by a variety of oncogene signals, JRE-IL6 could not be activated by activated Ha-Ras, Raf-1, or 12-0-tetradecanoylphorbol-13-acetate. We show that IL-6 activates JRE-IL6 through an H7-sensitive pathway that does not involve protein kinase C, cyclic AMP-dependent kinase, Ca2+ - or calmodulin-dependent kinases, Ras, Raf-1, or NF-IL6 (C/EBPbeta). The combination of JEBS and the CRE-like site appears to form the basis for the selective and efficient response of JRE-IL6 to IL-6 signals, but not to signals generated by activated Ha-Ras, Raf-1, or protein kinase C.
引用
收藏
页码:3027 / 3041
页数:15
相关论文
共 88 条
[1]   A NUCLEAR FACTOR FOR IL-6 EXPRESSION (NF-IL6) IS A MEMBER OF A C/EBP FAMILY [J].
AKIRA, S ;
ISSHIKI, H ;
SUGITA, T ;
TANABE, O ;
KINOSHITA, S ;
NISHIO, Y ;
NAKAJIMA, T ;
HIRANO, T ;
KISHIMOTO, T .
EMBO JOURNAL, 1990, 9 (06) :1897-1906
[2]   RECOMBINANT HUMAN B-CELL STIMULATORY FACTOR-II (BSF-2/IFN-BETA2) REGULATES BETA-FIBRINOGEN AND ALBUMIN MESSENGER-RNA LEVELS IN FAO-9 CELLS [J].
ANDUS, T ;
GEIGER, T ;
HIRANO, T ;
NORTHOFF, H ;
GANTER, U ;
BAUER, J ;
KISHIMOTO, T ;
HEINRICH, PC .
FEBS LETTERS, 1987, 221 (01) :18-22
[3]   REGULATION OF THE JUNB GENE BY V-SRC [J].
APEL, I ;
YU, CL ;
WANG, T ;
DOBRY, C ;
VANANTWERP, ME ;
JOVE, R ;
PROCHOWNIK, EV .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (08) :3356-3364
[4]   GROWTH-FACTORS AND MEMBRANE DEPOLARIZATION ACTIVATE DISTINCT PROGRAMS OF EARLY RESPONSE GENE-EXPRESSION - DISSOCIATION OF FOS AND JUN INDUCTION [J].
BARTEL, DP ;
SHENG, M ;
LAU, LF ;
GREENBERG, ME .
GENES & DEVELOPMENT, 1989, 3 (03) :304-313
[6]   THE PRODUCT OF THE C-ETS-1 PROTOONCOGENE AND THE RELATED ETS2 PROTEIN ACT AS TRANSCRIPTIONAL ACTIVATORS OF THE LONG TERMINAL REPEAT OF HUMAN T-CELL LEUKEMIA-VIRUS HTLV-1 [J].
BOSSELUT, R ;
DUVALL, JF ;
GEGONNE, A ;
BAILLY, M ;
HEMAR, A ;
BRADY, J ;
GHYSDAEL, J .
EMBO JOURNAL, 1990, 9 (10) :3137-3144
[7]   SERUM-INDUCED, TPA-INDUCED, AND RAS-INDUCED EXPRESSION FROM AP-1/ETS-DRIVEN PROMOTERS REQUIRES RAF-1 KINASE [J].
BRUDER, JT ;
HEIDECKER, G ;
RAPP, UR .
GENES & DEVELOPMENT, 1992, 6 (04) :545-556
[8]   REGULATED EXPRESSION OF 3 C/EBP ISOFORMS DURING ADIPOSE CONVERSION OF 3T3-L1 CELLS [J].
CAO, ZD ;
UMEK, RM ;
MCKNIGHT, SL .
GENES & DEVELOPMENT, 1991, 5 (09) :1538-1552
[9]   GROWTH-FACTOR SIGNALING - WHERE IS THE SPECIFICITY [J].
CHAO, MV .
CELL, 1992, 68 (06) :995-997
[10]   A NEW CYTOKINE RECEPTOR SUPERFAMILY [J].
COSMAN, D ;
LYMAN, SD ;
IDZERDA, RL ;
BECKMANN, MP ;
PARK, LS ;
GOODWIN, RG ;
MARCH, CJ .
TRENDS IN BIOCHEMICAL SCIENCES, 1990, 15 (07) :265-270