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KIAA1199 interacts with glycogen phosphorylase kinase β-subunit (PHKB) to promote glycogen breakdown and cancer cell survival.

Terashima M, Fujita Y, Togashi Y, Sakai K, De Velasco MA, Tomida S, Nishio K - Oncotarget (2014)

Bottom Line: The KIAA1199 gene was first discovered to be associated with non-syndromic hearing loss.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.

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.

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Related in: MedlinePlus

mRNA expression levels of KIAA1199The mRNA expression levels were determined using a real-time RT-PCR analysis in (A) human normal tissues, (B) human cancer cell lines. GAPDH was used to normalize the expression levels. The data shown represent the average ± SD of three independent experiments.
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Figure 1: mRNA expression levels of KIAA1199The mRNA expression levels were determined using a real-time RT-PCR analysis in (A) human normal tissues, (B) human cancer cell lines. GAPDH was used to normalize the expression levels. The data shown represent the average ± SD of three independent experiments.

Mentions: To examine the tissue distribution of KIAA1199 mRNA, we performed real-time RT PCR using 24 normal human tissue samples. High expression levels of KIAA1199 mRNA were detected in the brain, placenta, and lung, whereas the levels in the liver, peripheral blood, bone marrow, and skeletal muscle were relatively low (Figure1A). These results were mostly consistent with a previous report describing the results of northern blotting [5], except that we additionally detected KIAA1199 mRNA in the prostate and spinal cord. KIAA1199 expression was also examined in 62 human cancer cell lines (Fig 1B). A relatively high mRNA expression level was observed in gastric cancer (TU-KATO III, okajima, and HSC43), colorectal cancer (Colo201 and COCM-1), pancreatic cancer (sui73), and lung cancer (H520). These results suggest that KIAA1199 is expressed in a variety of cancers especially those of digestive organs, such as stomach or colon (Figure 1B).


KIAA1199 interacts with glycogen phosphorylase kinase β-subunit (PHKB) to promote glycogen breakdown and cancer cell survival.

Terashima M, Fujita Y, Togashi Y, Sakai K, De Velasco MA, Tomida S, Nishio K - Oncotarget (2014)

mRNA expression levels of KIAA1199The mRNA expression levels were determined using a real-time RT-PCR analysis in (A) human normal tissues, (B) human cancer cell lines. GAPDH was used to normalize the expression levels. The data shown represent the average ± SD of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196182&req=5

Figure 1: mRNA expression levels of KIAA1199The mRNA expression levels were determined using a real-time RT-PCR analysis in (A) human normal tissues, (B) human cancer cell lines. GAPDH was used to normalize the expression levels. The data shown represent the average ± SD of three independent experiments.
Mentions: To examine the tissue distribution of KIAA1199 mRNA, we performed real-time RT PCR using 24 normal human tissue samples. High expression levels of KIAA1199 mRNA were detected in the brain, placenta, and lung, whereas the levels in the liver, peripheral blood, bone marrow, and skeletal muscle were relatively low (Figure1A). These results were mostly consistent with a previous report describing the results of northern blotting [5], except that we additionally detected KIAA1199 mRNA in the prostate and spinal cord. KIAA1199 expression was also examined in 62 human cancer cell lines (Fig 1B). A relatively high mRNA expression level was observed in gastric cancer (TU-KATO III, okajima, and HSC43), colorectal cancer (Colo201 and COCM-1), pancreatic cancer (sui73), and lung cancer (H520). These results suggest that KIAA1199 is expressed in a variety of cancers especially those of digestive organs, such as stomach or colon (Figure 1B).

Bottom Line: The KIAA1199 gene was first discovered to be associated with non-syndromic hearing loss.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.

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.

Show MeSH
Related in: MedlinePlus