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

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.
AuthorsMasato Terashima, Yoshihiko Fujita, Yosuke Togashi, Kazuko Sakai, Marco A De Velasco, Shuta Tomida, Kazuto Nishio
JournalOncotarget (Oncotarget) Vol. 5 Issue 16 Pg. 7040-50 (Aug 30 2014) ISSN: 1949-2553 [Electronic] United States
PMID25051373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Protein Subunits
  • Proteins
  • Glycogen
  • Phosphorylase Kinase
  • CEMIP protein, human
  • Hyaluronoglucosaminidase
Topics
  • Apoptosis (physiology)
  • Cell Line, Tumor
  • Cell Survival (physiology)
  • Glycogen (metabolism)
  • Humans
  • Hyaluronoglucosaminidase
  • Liver Neoplasms (enzymology, genetics, metabolism, pathology)
  • Phosphorylase Kinase (genetics, metabolism)
  • Protein Subunits
  • Proteins (genetics, metabolism)
  • Stomach Neoplasms (enzymology, genetics, metabolism, pathology)
  • Transfection
  • Up-Regulation

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