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MCEF is localized to the nucleus by protein sequences encoded within three distinct exons, where it represses HIV-1 Tat-transactivation of LTR-directed transcription.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2007 Mar 01; Vol. 3 (4), pp. 225-36. Date of Electronic Publication: 2007 Mar 01. - Publication Year :
- 2007
-
Abstract
- Translocations between the human Mixed Lineage Leukemia (MLL) and AF4 Family (AFF) member genes, are implicated in leukemia. Mutations to AFFs can disrupt lymphopoesis, CNS development and spermatogenesis. However, despite the growing list of pathologies linked to AFF members, their evolutionary relationship and the structure/function of individual members, remain to be elucidated. Here, we first report that database mining and phylogenetic analysis with AFF proteins from multiple species, revealed two monophyletic sister clades, suggesting a common Bilateria ancestor. We then examined the structure/function of the most recently discovered AFF member, MCEF (also known as AF5q31 or AFF4). In silico, the human MCEF gene was found to have 21 exons, and code for a protein with seven nuclear localization sequences (NLS). In HeLa cells, an MCEF-EGFP fusion protein, localized exclusively to the nucleus. Consequently, we made twenty constructs, expressing MCEF deletion mutants fused to EGFP and/or DsRed fluorescent proteins. Three distinct protein sequences, encoded by three separate MCEF exons, were found to mediate nuclear localization, only two of which were predicted in silico. Importantly, we also found that ectopic expression of MCEF, repressed HIV-1 LTR-directed RNA Polymerase II transcription, at the level of Tat-transactivation. We suggest that portions of MCEF could be exploited for chimeric transcription factor repression (CTFR) of HIV-1.
- Subjects :
- Active Transport, Cell Nucleus
Amino Acid Sequence
Animals
Consensus Sequence
DNA, Complementary genetics
Evolution, Molecular
Exons genetics
Genes, Reporter
HIV Long Terminal Repeat
HeLa Cells
Humans
Invertebrates genetics
Molecular Sequence Data
Nuclear Proteins classification
Phylogeny
RNA Polymerase II metabolism
RNA Splicing
Recombinant Fusion Proteins metabolism
Repressor Proteins chemistry
Repressor Proteins genetics
Sequence Analysis, DNA
Sequence Homology
Species Specificity
Transcription Factors chemistry
Transcription Factors genetics
Transcriptional Elongation Factors
Vertebrates genetics
tat Gene Products, Human Immunodeficiency Virus
Gene Products, tat antagonists & inhibitors
HIV-1 physiology
Nuclear Proteins genetics
Repressor Proteins physiology
Transcription Factors physiology
Transcriptional Activation
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 3
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 17389929
- Full Text :
- https://doi.org/10.7150/ijbs.3.225