GABP cooperates with c-Myb and C/EBP to activate the neutrophil elastase promoter

被引:70
作者
Nuchprayoon, I
Simkevich, CP
Luo, ML
Friedman, AD
Rosmarin, AG
机构
[1] MIRIAM HOSP,DIV HEMATOL ONCOL,PROVIDENCE,RI 02906
[2] JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,DIV PEDIAT ONCOL,BALTIMORE,MD 21205
[3] BROWN UNIV,DEPT MED,DIV HEMATOL,PROVIDENCE,RI 02912
关键词
D O I
10.1182/blood.V89.12.4546
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Neutrophil elastase (NE) is a serine protease that is transcriptionally regulated during early myeloid differentiation. The murine NE (mNE) promoter contains functionally important c-Myb, C/EBP, and ets binding sites. Deletion of the ets site reduced promoter activity by 90%. Although the ets transcription factor, PU.1, bound to this ets site, it only modestly activated the mNE promoter. Here, we show that a second transcription factor from myeloid cells - GABP - binds to the mNE ets site but strongly activates the mNE promoter. GABP is a heteromeric transcription factor complex that consists of GABP alpha, an ets factor, and GABP beta, a Notch-related protein. GABP alpha bound to the mNE ets site and, in turn, recruited GABP beta to form a transcriptionally active complex. GABP alpha and PU,1 competed with each other for binding to the mNE ets site. GABP increased the activity of the mNE promoter sevenfold in U937 myeloid cells. GABP cooperated with c-Myb and C/EBP alpha to activate the mNE promoter more than 85-fold in otherwise nonpermissive, nonhematopoietic NIH 3T3 cells. Thus, GABP binds to the crucial mNE promoter ets site and powerfully activates its expression alone and in cooperation with the transcription factors c-Myb and C/EBP. (C) 1997 by The American Society of Hematology.
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页码:4546 / 4554
页数:9
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