title: HBXAP, a novel PHD-finger protein, possesses transcription repression activity.
abstract: The PHD/LAP (plant homology domain/leukemia associated protein) finger motif is characteristically defined by a histidine and seven cysteines that are spatially arranged in a C4HC3 consensus sequence. This unique zinc finger, found primarily in a wide variety of chromatin-associated proteins, is considered to mediate protein-protein interactions. We have isolated a novel human PHD-finger protein, HBXAP (for hepatitis B virus x associated protein). HBXAP has three alternatively spliced isoforms. We also identified the Drosophila melanogaster HBXAP ortholog, gene CG8677. Based on alignment of four different proteins, we found a novel conserved domain in HBXAP that we designated the HBXAP conserved domain (XCD). We show that HBXAP represses transcription when recruited to DNA via the DNA binding of GAL4. Furthermore, the PHD finger alone suffices to repress transcription, thus attributing a functional role to this domain. The gene HBXAP is localized to the long arm of human chromosome 11 between q13.4 and q14.1. This region is amplified and rearranged in many tumors, suggesting a role for HBXAP in tumorigenesis similar to that of other PHD-containing proteins.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Shamay
authors.forename: Orr
authors.initials: O
authors.lastname: Barak
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shaul
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D015536:Down-Regulation; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D016415:Sequence Alignment; D017385:Sequence Homology; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D009687:Nuclear Proteins; D020033:Protein Isoforms; C452851:RSF1 protein, human; D015534:Trans-Activators