Rabbit Anti-Human SSBP2 Polyclonal Antibody

The human single-stranded DNA binding Protein 2 (SSBP2) is a tumor suppressor implicated in multiple cancer forms. The SSBP2 and related SSBP3/SSBP4 proteins are predicted to be intrinsically disordered excepted for their highly conserved N-terminal LUFS (LUG/LUH, Flo8, and SSBP/SSDP) domain. LUFS domains are found in a number of proteins including some transcriptional co-repressors. Although LUFS domains contain an N-terminal Lis homology (LisH) motif that typically forms a stable dimer, no 3D structure of any LUFS domain is available. Here, we report a crystal structure of the LUFS domain of human SSBP2 at 1.52 angstrom resolution. We show that the SSBP2 LUFS domain forms a homo-tetramer and reveal how an alpha-helix C-terminal to the LisH motif mediates SSBP2 tetramerization (dimerization of dimers). Conservation of the tetramerization interface among LUFS domains suggests that other LUFS domains may also form tetramers in similar manners.

Acute myelogenous leukemia (AML) is the most common leukemia in adults with clonal proliferation of myeloid stem cells. Two or more cooperating mechanisms, namely block in differentiation, enhanced proliferation and resistance to programmed cell death, underlie this neoplastic transformation. Nonrandom, complete and partial deletions of chromosome 5 are common anomalies in AML. Using positional cloning strategies, we characterized an evolutionarily conserved candidate myeloid leukemia suppressor gene encoding sequence-specific single-stranded DNA binding protein 2 ( SSBP2) from chromosome 5q13.3, a locus that is frequently deleted in AML. Recent studies in Drosophila and Xenopus demonstrate a pivotal role for SSBPs in embryonic differentiation. In mammals, SSBP2 is one of three highly related and ubiquitously expressed genes. Here, we identify frequent loss of SSBP2 protein expression in human AML cell lines using highly specific antibodies. Furthermore, inducible expression of SSBP2 in the AML cell line U937 leads to loss of clonogenicity, G1 arrest and partial differentiation. Remarkably, inducible expression of SSBP2 is accompanied by downregulation of C-MYC expression. Our findings are consistent with human SSBP2 being a novel regulator of hematopoietic growth and differentiation, whose loss confers a block in differentiation advantage to myeloid leukemic cells.