The BTB Domain of bric à brac Mediates Dimerization In Vitro

Abstract

The gene bric à brac (bab) is required for the proper development of the limbs and ovary in Drosophila melanogaster. bab encodes a BTB domain (also called a POZ domain), an ϳ115-amino-acid conserved motif found primarily in the N termini of zinc finger proteins. In this paper, we show that the BTB domain of bab can mediate protein dimerization in vitro. In addition, we demonstrate that the first 51 amino acids of the bab BTB domain are sufficient for dimerization, and we identify amino acids within this region that are required for binding.The gene bric à brac (bab) is required for the proper development of the limbs and ovary in Drosophila melanogaster (13,14,28). bab, which encodes a nuclear protein, has a homeotic mutant phenotype in the leg and is expressed in a discontinuous gradient along the proximal-distal axis of the tarsus. bab is also expressed in and required for the development of the terminal filaments in the larval ovary. Because terminal filaments are required for ovariole development, mutations in bab result in disorganized ovaries and female sterility.bab encodes a BTB domain, an evolutionarily conserved motif of ϳ115 amino acids found in an increasing number of proteins having a variety of functions ( Fig. 1) (13,38). The Drosophila genome contains a group of genes encoding highly conserved BTB domains, many of which have been shown to encode zinc finger domains and function as transcriptional regulators. Southern analysis suggests that there are at least 40 of these BTB domain-encoding genes in D. melanogaster (38). Other Drosophila proteins with less conserved BTB domains include kelch, a cytoplasmic protein that functions during oogenesis (34), and germ cell-less, which is found in the nuclear pores of pole cells (17,18). A number of vertebrate zinc finger proteins also contain BTB domains, including KUP (5), ZFPJS (31), ZF5 (25), ZID (2), and FBP (23). Two genes involved in human cancer also encode BTB domains: BCL-6 (35), also called LAZ3 (20), and BCL-5 (24), which is located at the sites of chromosome translocations associated with diffuse large-cell lymphoma and is thought to be the proto-oncogene specifically involved in the pathogenesis of this lymphoma. The PLZF gene is located at the sites of chromosome translocations associated with acute promyelocytic leukemia (6, 7). Several BTB domain-encoding genes in Caenorhabditis elegans and in poxviruses have been identified by genomic sequence analysis. Neither the C. elegans nor the poxvirus genes have been found to encode zinc fingers or any other known DNA binding motifs, and the functions of these genes are unknown (4,16,21,29,32,33).The BTB domain defines a family of proteins with varied activities. Understanding the function of this domain should provide a key step toward the characterization of this family. We have begun a functional analysis of the BTB domain of bab. In this paper we show that one activity of the bab BTB domain is dimerization and that this activity is restricted to the N-terminal half of the domain. This is consi...

ENC-1: A Novel MammalianKelch-Related Gene Specifically Expressed in the Nervous System Encodes an Actin-Binding Protein

“…This domain, found primarily in zinc finger proteins, is called BTB/ POZ and defines a newly characterized proteinprotein interaction interface (Godt et al, 1993;Bardwell and Treisman, 1994;Zollman et al, 1994). This domain mediates both dimer and heterodimer formation in vitro (for review, see Albagli et al, 1995) (Chen et al, 1995). The presence of the BTB/ POZ domain could allow ENC-1 homodimerization resulting in a complex with two actin-binding domains that could cross-link and stabilize actin filaments.…”

Printor, a Novel TorsinA-interacting Protein Implicated in Dystonia Pathogenesis

“…1D). Printor also contains an N-terminal region with homology to the BTB (broad complex, tramtrack, and bric a brac) domain (also known as POZ (poxvirus and zinc finger) domain), a protein-protein interaction domain that can mediate dimerization (49) or binding to cullin3, a component of a multisubunit E3 ubiquitin-protein ligase complex (50). It is unclear whether this region is a functional BTB domain because it is interrupted by the insertion of a 48-amino acid proline/glutamine (P/Q)-rich sequence (Fig.…”

Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene

“…The BTB/POZ domain is also present in some viral (Koonin et al, 1992) and cellular proteins (Xue and Cooley, 1993), which do not possess any obvious DNA binding motifs and whose function may not be associated with transcription. The BTB/ POZ domain has been shown to be sucient in mediating self-association of a number of BTB/POZ domain proteins (Bardwell and Treisman, 1994;Chen et al, 1995), including LAZ-3/BCL-6 and PLZF (Dong et al, 1996), and in mediating transcriptional repression when fused to a heterologous DNA-binding region (Chang et al, 1996;Li et al, 1997;Seyfert et al, 1996). In addition, for a number of POK proteins, the BTB/POZ domain appears to confer speci®c, often speckled, nuclear localization pattern (Bardwell and Treisman, 1994;Dhordain et al, 1995;Dong et al, 1996).…”