REKLES is an ARID3-restricted multifunctional domain.
Bright/Dril1/ARID3a is a B cell-specific, matrix association (or attachment) region-binding transcriptional regulator of immunoglobulin heavy chain genes and of E2F1-dependent cell cycle progression. Bright contains a central DNA binding domain termed ARID (AT-rich interacting domain) and a C-terminal region termed REKLES (for a conserved amino acid motif). The ARID domain has been identified in seven highly conserved families of metazoan proteins (ARID1-5 and JARID1-2), whereas REKLES is found only in the ARID3 subfamily (composed of Bright/ARID3a, Bdp/ARID3b, and Bright-like/ARID3c). REKLES consists of two subdomains: a modestly conserved N-terminal REKLESalpha and a highly conserved (among ARID3 orthologous proteins) C-terminal REKLESbeta. Previously we showed that Bright undergoes nucleocytoplasmic shuttling and that REKLESalpha and -beta were required, respectively, for nuclear import and Crm1-dependent nuclear export. Here we show that Bright further requires REKLESbeta for self-association or paralogue association and for nuclear matrix targeting. REK-LES promotes and regulates the extent of Bright multimerization, which occurs in the absence or presence of target DNA and is necessary for specific DNA binding. REKLESbeta-mediated interaction of Bright with Bdp, which localizes strictly to the nucleus, traps Bright within the nucleus via neutralization of its nuclear export activity. These results identify REKLES as a multifunctional domain that has co-evolved with and regulates functional properties of the ARID3 DNA binding domain.
Kim
Dongkyoon
D
Section of Molecular Genetics and Microbiology and Institute of Cell and Molecular Biology, University of Texas, Austin, Texas 78712-0162, USA.
Probst
Loren
L
Das
Chhaya
C
Tucker
Philip W
PW
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D015530:Nuclear Matrix / Q000235:genetics / Q000378:metabolism; D009857:Oncogenes / Q000235:genetics*; D009928:Organ Specificity / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors
C490798:ARID3A protein, human; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D007143:Immunoglobulin Heavy Chains; D015800:Protozoan Proteins; D015534:Trans-Activators; D014157:Transcription Factors