Upstream regions of thec-junpromoter regulate phorbol ester-induced transcription in U937 leukemic cells

Abstract

To understand the mechanism by which phorbol esters (PMA) stimulate c-jun transcription in human leukemic cell line U937, we have mutated specific enhancer sequences within the c-jun promoter. We find in the region of DNA from -132 to +170 containing Sp1, C-TF and AP-1 sequences that mutation of the AP-1 sequence alone is not sufficient to abrogate transcription, and mutation of the Sp1 sequence increases transcription 4-fold. Although mutation of the CTF site had no effect, CTF and AP-1 mutations together totally abrogate PMA-induced transcription. In comparison mutations of either of these sites alone or together in a construct containing -1639/+740 of the c-jun promoter had no effect on transcription. Because this data suggested the possibility of other upstream control regions, we sequenced the promoter from -142 to -1639. This sequence demonstrates a greater than 70% homology between human, and mouse c-jun promoters for the region from -142 to -441, and a second AP-1-like site in the -183 to -192 region. Mutation of this site did not influence transcription by PMA. By making constructs containing varying portions of the promoter, we have identified the region between -142 and -711 to be responsible for mediating PMA-induced c-jun transcription.

Sp1 Deacetylation Induced by Phorbol Ester Recruits p300 To Activate 12(S)-Lipoxygenase Gene Transcription

“…4C). The profile of this kinetic change was similar to that seen in c-Jun protein biosynthesis induced by PMA (39). Recruitment of HDAC1 was significantly increased at 3 h but then decreased even below the basal level 6 h after the PMA stimulation (Fig.…”

Hypoxia Promotes Nuclear Translocation and Transcriptional Function in the Oncogenic Tyrosine Kinase RON

“…from the transcription start site. This regulatory region is different from conventional À200 upstream from the transcription start site under normoxia (39,42,43).…”

Downregulation of c-Jun Expression by Transcription Factor C/EBPα Is Critical for Granulocytic Lineage Commitment

“…The proximal AP-1 site (pAP-1) in the promoter lies within the region from bp Ϫ180 to Ϫ63. Earlier studies with the human c-Jun promoter addressed the importance of the proximal AP-1 site in c-Jun promoter being sufficient for a maximal response to various signals (TPA, serum, UV, E1A, and IL-1) (18,49). Using the human c-Jun promoter, we show that C/EBP␣ blocks the autoactivation capacity of c-Jun through the proximal AP-1 site.…”

“…The level of c-Jun expression is regulated by both transcriptional and posttranscriptional mechanisms. Among important regulatory elements previously identified in the c-Jun promoter, there are two AP-1 sites, a proximal AP-1 site (pAP-1) located between bp Ϫ71 and Ϫ64 and a distal AP-1 site (dAP-1) located between bp Ϫ190 and Ϫ183 in the c-Jun promoter (1,46,49). Importantly, c-Jun is autoregulated by its product Jun/AP-1 (1).…”