Open AccessA 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
Author(s) -
Kropotov Andrey,
Sedova Vanda,
Ivanov Vadim,
Sazeeva Natalya,
Tomilin Alexey,
Krutilina Raisa,
Oei Shiao Li,
Griesenbeck Joachim,
Buchlow Gerhard,
Tomilin Nikolai
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00162.x
Subject(s) - biology , rna polymerase iii , microbiology and biotechnology , repressor , transcription (linguistics) , gatad2b , gene , rna , transcription factor , rna polymerase , genetics , linguistics , philosophy
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.