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- W1973809627 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCIIp45 (aka MIIP) is a newly discovered gene whose protein product inhibits cell migration. HDAC6 is a class IIb deacetylase that specifically deacetylates α-tubulin, modulates microtubule dynamics and promotes cell migration. A yeast two-hybrid assay using IIp45 as the bait identified HDAC6 protein as a binding partner of IIp45. This physical interaction of the two functionally antagonizing proteins was confirmed by Glutathione S-transferase (GST) pull-down assay and co-immunoprecipitation (Co-IP) assay in human cells. Serial deletion constructs of HDAC6 were used to characterize the interaction of HDAC6 and IIp45, and this analysis found that the two catalytic domains of HDAC6 protein were required for IIp45 binding. We examined the protein expression patterns of IIp45 and HDAC6 in glioma tissues. Elevated protein levels of HDAC6 were found in high grade glioma samples in contrast to the decreased protein expression of IIp45. The potential negative regulation of HDAC6 expression by IIp45 was confirmed in cell lines with altered IIp45 expression by constitutive overexpression or small interfering RNA knockdown. Protein turnover study revealed that overexprsssion of IIp45 significantly reduced intracellular protein stability of endogenous HDAC6, indicating a possible mechanism for the negative regulation of HDAC6 by IIp45. Results from the HDAC activity assay demonstrated that overexpressed IIp45 effectively decreased HDAC6 activity, increased acetylated α-tubulin, and reduced cell migration. The increased cell migration by siIIp45 knockdown was significantly reversed by co-transfection of siHDAC6. Thus, we report here for the first time a novel mechanism by which IIp45 inhibits cell motility through inhibition of HDAC6Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5294." @default.
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- W1973809627 date "2010-04-15" @default.
- W1973809627 modified "2023-09-26" @default.
- W1973809627 title "Abstract 5294: IIp45 inhibits cell migration through inhibition of HDAC6" @default.
- W1973809627 doi "https://doi.org/10.1158/1538-7445.am10-5294" @default.
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