HSPC038 - expression, structure and function

HSPC038 was first described as a protein expressed in CD34+ human stem/progenitor cells (HSPC) and shown to be differentially expressed in various hematopoietic cell lines. Phylogenetic analysis of the HSPC038 protein revealed strong evolutionary conservation within bilateria. The C. elegans homolog of HSPC038 - termed Nx - is located in an operon together with the C. elegans homolog of ICln, a multifunctional protein that can act as an ion channel and as a scavenger of splicing factors. Most interestingly, it could be shown in C. elegans that HSPC038/Nx and ICln are not only transcribed into a common mRNA, but also interact functionally with each other. Fascinatingly, the interaction between HSPC038/Nx and ICln observed in C. elegans is also conserved in human cells, which strongly suggests that the role of the HSPC038-ICln module is of major physiological importance. In line with this observation is the finding that downregulation of HSPC038/Nx in C. elegans by RNAi leads to growth retardation, and knock-out of ICln in both C. elegans and mammalian cells is lethal. Although HSPC038 and the HSPC038-ICln module are evidently of major physiological importance, the expression pattern in mammalian cells and organs as well as the physiological role of HSPC038 and the HSPC038-ICln-module are essentially unknown. It is, therefore, the aim of this study to characterize the expression profile and function of HSPC038, as well as the functional significance of the conserved HSPC038-ICln interaction in mammalian cells.

HSPC038 was first described as a protein expressed in CD34+ human stem/progenitor cells (HSPC) and shown to be differentially expressed in various hematopoietic cell lines. Phylogenetic analysis of the HSPC038 protein revealed strong evolutionary conservation within bilateria. The C. elegans homolog of HSPC038 - termed Nx - is located in an operon together with the C. elegans homolog of ICln, a multifunctional protein that can act as an ion channel and as a scavenger of splicing factors. Most interestingly, it could be shown that in C. elegans, HSPC038/Nx and ICln are not only transcribed from a common mRNA, but also interact functionally with each other. Fascinatingly, the interaction between HSPC038/Nx and ICln observed in C. elegans is also conserved in human cells, which strongly suggests that the role of the HSPC038-ICln module is of major physiological importance. In line with this observation is the finding that downregulation of HSPC038/Nx in C. elegans by RNAi leads to growth retardation, and knock-out of ICln in both C. elegans and mammalian cells is lethal. Although HSPC038 and the HSPC038-ICln module are evidently of major physiological importance, the physiological role of HSPC038 and the HSPC038-ICln-module is essentially unknown. It was, therefore, the aim of the study to characterize the expression profile and function of HSPC038, as well as the functional significance of the conserved HSPC038-ICln interaction in mammalian cells.