Abstract:
:This study investigates the transcriptional role of the human mitochondrial carnitine/acylcarnitine carrier (CAC) proximal promoter. Through deletion analysis, an activation domain (-334/-80 bp) was identified which contains FOXA and Sp1 active sites. The wild-type (but not mutated) -334/-80 bp region of the CAC gene conferred 74% LUC transgene activity in HepG2 cells, 17% in HEK293 cells and 14% in SK-N-SH cells as compared to that observed with the entire -1503/+3 bp proximal promoter. Overexpression and silencing of FOXA2 or Sp1 in HepG2 cells enhanced and diminished, respectively, LUC activity, CAC transcript and CAC protein. In HEK293 and SK-N-SH cells, which do not contain FOXA1-3, LUC activity was increased by FOXA2 overexpression to a greater extent than in HepG2 cells. Both FOXA2 and Sp1 in HepG2, and only Sp1 in HEK293 and SK-N-SH cells, were found to be bound to the CAC proximal promoter. These results show that FOXA and Sp1 sites in HepG2 cells and only the Sp1 site in HEK293 and SK-N-SH cells have a critical role in the transcriptional regulation of the CAC proximal promoter.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Convertini P,Infantino V,Bisaccia F,Palmieri F,Iacobazzi Vdoi
10.1016/j.bbrc.2010.11.126subject
Has Abstractpub_date
2011-01-07 00:00:00pages
376-81issue
1eissn
0006-291Xissn
1090-2104pii
S0006-291X(10)02201-1journal_volume
404pub_type
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