Abstract
The KIAA1199 gene was first discovered to be associated with non-syndromic hearing loss. Recently, several reports have shown that the up-regulation of KIAA1199 is associated with cancer cell migration or invasion and a poor prognosis. These findings indicate that KIAA1199 may be a novel target for cancer therapy. Therefore, we explored in detail the function of KIAA1199 in cancer cells. In this study, we investigated the interaction of KIAA1199 protein with intracellular proteins in cancer cells. To this end, we expressed KIAA1199-MBP fusion protein and performed a pull-down assay. In addition, KIAA1199-overexpressing cancer cell lines were constructed using a retroviral vector and were used for further experiments. A pull-down analysis showed that the glycogen phosphorylase kinase β-subunit (PHKB) interacted with the C-terminal region of KIAA1199 protein. Furthermore, we observed the interaction of KIAA1199 with glycogen phosphorylase brain form (PYGB) under serum-free conditions. The interaction promoted glycogen breakdown and cancer cell survival. Our findings indicate that KIAA1199 plays an important role in glycogen breakdown and cancer cell survival and that it may represent a novel target for cancer therapy.
Highlights
The KIAA1199 gene is located on chromosome 15q25 and encodes a 150-kDa protein (1361 amino acids) that was first described as an inner ear protein in which three point mutations were found to be associated with non-syndromic hearing loss [1]
Immunoprecipitation showed a moderate interaction of KIAA1199 with PYGB under serum-free conditions (Figure 4C). These results suggest that KIAA1199 interacts with PYGB directly or indirectly through phosphorylase kinase β-subunit (PHKB), resulting in the enhanced phosphorylation of PYGB under serum-free conditions
The inner cell mass of a tumor is exposed to nutrient deprivation and hypoxia; glucose concentrations were much lower in tumor tissues than in normal tissues in both gastric cancer and colorectal cancer patients [16]
Summary
The KIAA1199 gene is located on chromosome 15q25 and encodes a 150-kDa protein (1361 amino acids) that was first described as an inner ear protein in which three point mutations were found to be associated with non-syndromic hearing loss [1]. It has a G8 domain, containing eight conserved glycine residues and consisting of five β-strand pairs and one α-helix, four pbH1 domains, consisting of parallel β-helix repeats, and two GG domains, each consisting of seven β-strands and two α-helices. KIAA1199 has been shown to play an important role in the growth and invasiveness of breast cancer cells [7]
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