Characterization of human cysteine-rich protein, a member of the lim/double zinc-finger family, as a primary response gene

Abstract

Human cysteine-rich protein (hCRP) is a highly conserved and widely distributed 23.4 kDa zinc finger protein. The unusual zinc fingers of hCRP constitute a highly characteristic 52 amino acid motif referred to as the LIM/double zinc finger motif, (CXXC-X\sb{17-19}HXXC)-XX-(CXXC-X\sb{16-20}-CXXC/D/H), shared with a number of proteins that are involved in transcriptional regulation and/or developmental control: mouse/rat cysteine-rich intestinal protein (CRIP), rhombotin, rIsl-1, lin-11, mec-3, and Xlim-1. The characterization of crp as a primary response gene to serum stimulation in quiescent mouse and human cells suggests that crp may play a regulatory role in the cell cycle. The crp mRNA induction profile is remarkably parallel to that of c-myc in both human and mouse cell lines upon serum stimulation. The 5\sp\prime-flanking sequence of the hcrp gene that shares several cis-regulatory elements with c-myc and other immediate early genes, and the parallel increases of the CRP protein with RNA levels upon serum stimulation further support the functional role of crp in the G\sb0 to S phase transition. The failure of hcrp promoter function assays to define a serum response element in the 5\sp\prime-flanking region may suggest a complicated regulatory mechanism for c-myc type immediate early genes. The cloning and characterization of the 23.2 kb hcrp gene, and the assignment of hcrp to human chromosome 1q24-1q32 provide valuable information for the future study of the biological function of this gene. Taking advantage of these primary studies, we found that crp may be involved in the oncogenesis of B-cell acute lymphoblastic leukemia (ALL) in our initial survey of B-cell ALL patients with chromosomal rearrangements in 1q21-1q32