DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC

Abstract

DEF-3(g16/NY-LU-12) encodes a novel RNA binding protein isolated by positional cloning from an SCLC homozygous deletion region in 3p21.3 and, in parallel, as a dierentially expressed gene during myelopoiesis from FDCPmix-A4 cells. DEF-3(g16/NY-LU-12) is ubiquitously expressed during mouse embryogenesis and in adult organs while human hematopoietic tissues showed dierential expression. The mouse and human proteins are highly conserved containing two RNA recognition motifs (RRMs) and other domains associated with RNA binding and protein-protein interactions. A database search identi®ed related proteins in human, rat, C. elegans and S. pombe including the 3p21.3 co-deleted gene, LUCA15. Recombinant proteins containing the RRMs of DEF-3(g16/NY-LU-12) and LUCA15 speci®-cally bound poly(G) RNA homopolymers in vitro. These RRMs also show similarity to those of the Hu protein family. Since anti-Hu RRM domain antibodies are associated with an anti-tumor eect and paraneoplastic encephalomyelitis, we tested sera from Hu syndrome patients with the RRMs of DEF-3(g16/NY-LU-12) and LUCA15. These were non-reactive. Thus, DEF-3(g16/ NY-LU-12) and LUCA15 represent members of a novel family of RNA binding proteins with similar expression patterns and in vitro RNA binding characteristics. They are co-deleted in some lung cancers and immunologically distinct from the Hu proteins.

3p21.3 Tumor Suppressor Gene H37/Luca15/RBM5 Inhibits Growth of Human Lung Cancer Cells through Cell Cycle Arrest and Apoptosis

“…This finding, although it needs to be validated by actual experiments, such as a gel-shift assay, is in a good correlation with the previous observations that the H37 protein contains RNA-binding motifs (i.e., RBM5 is another name for H37/Luca15; refs. 15,32), and H37 shows in vitro RNA-binding activity (33). Taken together, our current hypothesis is that H37 may function in some aspects of post-transcriptional regulations of certain important proteins involved in cell cycle and/or apoptosis (i.e., Bax, cyclin A, RB, etc.).…”

Up-regulation of the proapoptotic caspase 2 splicing isoform by a candidate tumor suppressor, RBM5

“…RBM5 is an RNA-binding protein containing two RNA recognition motifs (26,34). However, the cellular targets for RBM5 had not been reported.…”

LUCA-15-encoded sequence variants regulate CD95-mediated apoptosis

“…Full-length LUCA-15 protein contains a number of functional motifs, including two RNA binding domain motifs, two putative zinc-®nger DNA binding motifs, and a nuclear localization sequence. Recent studies have demonstrated that recombinant proteins containing LUCA-15 RNA binding motifs speci®cally bind poly(G) RNA homopolymers in vitro (Drabkin et al, 1999). Assuming that the splice variants delineated in Figure 2 are all part of translated sequences, and that these have the same start site as the LUCA-15 cDNA in the databanks, any protein encoded by the alternatively spliced LUCA-15 variant containing only the Je2 intron (Figure 2civ) would retain only RNA binding domain 1 (as there is a stop codon following exon 6).…”