Cloning, expression and characterization of a novel human MDSRP from CD34+ stem/progenitor cells
The myelodysplastic syndrome relative protein (MDSRP) gene was identified from human myelodysplastic syndrome (MDS) CD34+ cells. MDSRP contains 11 exons (3,535 bp; human chromosome 3q13.33) encoding a putative protein of 392 amino acids, with a highly conserved CAP10 domain, a hydrophobic signal peptide at its N-terminus, and an endoplasmic reticulum (ER) retention signal motif KTEL at the C-terminus. The homologs of MDSRP exist in different organisms from plants to the animal kingdom. Subcellular localization analysis showed that MDSRP is an ER–resident protein. MDSRP was expressed in most human adult tissues at different intensities, with lengths of 3.5kb and 1.9kb. A transcript of MDSRP was not detectable in colon, thymus, and small intestine, but it was abundant in liver, indicating that MDSRP may have an important physiological function in liver involving the regulation and development of haematopoietic stem/progenitor cells (HSPCs). MDSRP over-expressed U937 cells had a higher growth rate than cells lacking exogenic MDRSP protein expression, suggesting that MDSRP protein possesses the ability to promote cell proliferation. MDSRP specifically blocked the TGF-beta-induced expression of p15, but not p16. The study indicated that MDSRP may play an important role in the genesis of leukaemia.