Studies on an ALK related novel protein KIAA1618

KIAA1618/ALO17 is a novel protein discovered from the cases of the anaplastic large cell lymphoma (ALCL). A chimeric protein created due to a translocation of the N-terminal KIAA1618 protein (a.a. 1-1008) fused with the C-terminal truncated anaplastic lymphoma kinase (ALK, a.a. 1058-1620). According to the reported cases of ALCL, the oncogenesis is highly correlated with this chimeric protein. Nonetheless, the physiological function of KIAA1618 is still remained unclear. Using HA-tagged KIAA1618 to transfect HEK293 cells, silver-stain and Western blotting results showed that KIAA1618 migrated at approximate 170 kDa on SDS-PAGE which is much higher than an estimated 118.43 kDa from the predicted 1063 amino acids of KIAA1618 cDNA. Subcellular fraction and immunofluorescence staining revealed a predominant cytosolic distribution of KIAA1618. In vivo ubiquitination assay showed that KIAA1618 was poly-ubiquitinated with the addition of MG132, a proteasome inhibitor. A similar result was found when cells were exposed to some ER stress drugs. Moreover, apoptotic detections showed that KIAA1618 overexpressing HeLa cells were resistant to Tunicamycin and Thapsigargin treatment, an N-glycosylation inhibitor and a Ca2+ pump inhibitor, compared with control cells. Finally, a significant decrease in the expression level of Grp78 and PARP-1 cleavage was found in KIAA1618 overexpressing compared with control cells treated with Tunicamycin and Thapsigargin. Collectively, these results suggested that KIAA1618 may render cells resistance to ER stress.