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The identification and characterization of novel JMJD5 & Hdac1/Hdac2 interacting proteins

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The identification and characterization of novel JMJD5 & Hdac1/Hdac2 interacting proteins

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Samenvatting

Cancer is a genetic disease initiated by alterations in, for example, genes that regulate cell proliferation. These alterations may arise from genetic aberrations, which alter the function of gene encoding proteins, and aberrant epigenetic modifications such as acetylation, methylation and phosphorylation, which alter gene-expression patterns. The role of epigenetic modifications in tumorigenesis is poorly understood. Understanding of the epigenetic mechanisms, controlled by cancer-relevant histone modifying enzymes which counterbalance epigenetic modifications, will provide insight into the development of human diseases, including cancer. In order to obtain insight into the role of histone modifying enzymes in cancer, this study is focused on histone deacetylases HDAC1 and HDAC2, and histone demethylase JMJD5.
In this study, we have identified and partly characterized novel Hdac1 interacting proteins Wdr5, Npm1 and Dlat1 using a combination of GFP-tagged Hdac1/2 interactor overexpression, GFP-Trap® pull-down and western blot analysis. We showed that Dlat is a substrate for HDACs, which provides insight into a role for Hdac1 in regulation of the pyruvate decarboxylation step that links glycolysis to the citric acid cycle.
Furthermore, we have identified novel JMJD5 interacting proteins using a mass spectrometry-based proteomic approach. Many of the identified interactors have a role in metabolism, such as serine biosynthesis. In addition, we identified the JMJD5 interacting protein HCLS1-associated protein X-1, which is involved in the regulation of carcinoma cell migration and invasion. Future studies should provide insight into a possible role for JMJD5 in metabolism and/or carcinoma cell migration and invasion.

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OrganisatieAvans Hogeschool
AfdelingATGM Academie voor de technologie van Gezondheid en Milieu
PartnersThe Netherlands Cancer Institute - Antonie van Leeuwenhoek (NKI - AvL); Department of Gene Regulation
Datum2012-08
TypeBachelor
TaalEngels

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