Transcriptional regulation of the human mitochondrial peptide deformylase (PDF)

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Isabel Pereira Castro (Author) Other; Luis Teixeira da Costa (Author) Other; Antonio Amorim (Author) FCUP; Luisa Azevedo (Author) FCUP

Journal

Title: Biochemical and Biophysical Research Communications

Vol. 421

Pages: 825-831

ISSN: 0006-291X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 5 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-A07

DOI: 10.1016/j.bbrc.2012.04.097

Abstract (EN): The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formylmethionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7