Publikationsserver der RWTH Aachen University
Studies on a novel poly(ADP-ribosyl)ation polymerase PARP-10 and its functional interaction with c-Myc
Abstract
dc:descriptionThe c-Myc oncoprotein regulates different aspects of cell behavior by modulating gene expression. It was demonstrated that c-Myc stimulates cell proliferation, inhibits differentiation, and induces apoptosis. At the molecular level, c-Myc acts as a transcription factor by activating or repressing target genes. It is suggested that c-Myc exerts many functions by binding to other proteins, and several c-Myc-interaction partners play roles in the c-Myc-dependent regulation of gene expression and cell behavior. Thus, the characterization of novel c-Myc-binding proteins could give an insight into known as well as novel roles of c-Myc. To unterstand the function of c-Myc, a screen for novel interaction partners was performed by affinity column purifications, and PARP-10 was found to interact with c-Myc. PARP-10 is a member of the protein family of poly(ADP-ribose) polymerases (PARPs) that are protein-modifying and nucleotide-polymerizing enzymes able to catalyze the transfer of multiple ADP-ribose units from NAD+ to substrate proteins. Poly(ADP-ribosyl)ation has been reported to regulate many cellular processes such as DNA repair, genomic stability, cell cycle progression, cell death, and gene transcription. The aims of this study were to characterize PARP-10 biochemically and biologically, and to analyze the biochemical and functional interaction between c-Myc and PARP-10. This study shows that the novel PARP family member, PARP-10, is localized to the cytoplasm and the nucleus, PARP-10 contains a functional NES that mediates nuclear export which is CRM1-dependent. PARP-10 poly(ADP-ribosyl)ates itself and core histones, suggesting that it could play a potential role in the remodeling of chromatin. PARP-10 also reduces the proliferation rate of a PARP-10-inducible cell line, but shows no growth inhibitory effect on colony formation. The interaction of PARP-10 with the proto-oncoprotein c-Myc was shown in vivo and in vitro, furthermore the interaction occurs in the nucleus. c-Myc interacts with the C-terminus of PARP-10. PARP-10 can repress the c-Myc-dependent transactivation and inhibit c-Myc/Ha-Ras- and E1A/Ha-Ras-dependent transformation indicating that PARP-10 might repress c-Myc function in target gene regulation and oncogenesis. In summary, this study suggests that PARP-10 is a novel PARP enzyme that interacts with the proto-oncoprotein c-Myc. PARP-10 inhibits the c-Myc-dependent transactivation and transformation of rat embryo fibroblasts.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2005
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Yu, Mei
- Contributors dc:contributor
-
- Lüscher, Bernhard
Subjects
dc:subject × 8Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- eng
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:59973