A novel human DNA-binding protein with sequence similarity to a subfamily of redox proteins which is able to repress RNA-polymerase-III-driven transcription of the Alu-family retroposons in vitro.
In this study we identified a novel protein which may contribute to the transcriptional inactivity of Alu retroposons in vivo. A human cDNA clone encoding this protein (ACR1) was isolated from a human expression library using South-western screening with an Alu subfragment, implicated in the regulation of Alu in vitro transcription and interacting with a HeLa nuclear protein down-regulated in adenovirus-infected cells. Bacterially expressed ACR1 is demonstrated to inhibit RNA polymerase III (Pol III)-dependent Alu transcription in vitro but showed no repression of transcription of a tRNA gene or of a reporter gene under control of a Pol II promoter. ACR1 mRNA is also found to be down-regulated in adenovirus-infected HeLa cells, consistent with a possible repressor function of the protein in vivo. ACR1 is mainly (but not exclusively) located in cytoplasm and appears to be a member of a weakly characterized redox protein family having a central, highly conserved sequence motif, PGAFTPXCXXXXLP. One member of the family identified earlier as peroxisomal membrane protein (PMP)20 is known to interact in a sequence-specific manner with a yeast homolog of mammalian cyclosporin-A-binding protein cyclophilin, and mammalian cyclophilin A (an abundant ubiquitously expressed protein) is known to interact with human transcriptional repressor YY1, which is a major sequence-specific Alu-binding protein in human cells. It appears, therefore, that transcriptional silencing of Alu in vivo is a result of complex interactions of many proteins which bind to its Pol III promoter.
Kropotov
A
A
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
Sedova
V
V
Ivanov
V
V
Sazeeva
N
N
Tomilin
A
A
Krutilina
R
R
Oei
S L
SL
Griesenbeck
J
J
Buchlow
G
G
Tomilin
N
N
D000256:Adenoviridae; D020087:Alu Elements / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010920:Placenta / Q000201:enzymology; D012320:RNA Polymerase III / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018626:Retroelements / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D018626:Retroelements; C077832:SKO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012320:RNA Polymerase III