title: PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation.
abstract: The proto-oncoprotein c-Myc functions as a transcriptional regulator that controls different aspects of cell behavior, including proliferation, differentiation, and apoptosis. In addition, Myc proteins have the potential to transform cells and are deregulated in the majority of human cancers. Several Myc-interacting factors have been described that mediate part of Myc's functions in the control of cell behavior. Here, we describe the isolation of a novel 150 kDa protein, designated PARP-10, that interacts with Myc. PARP-10 possesses domains with homology to RNA recognition motifs and to poly(ADP-ribose) polymerases (PARP). Molecular modeling and biochemical analysis define a PARP domain that is capable of ADP-ribosylating PARP-10 itself and core histones, but neither Myc nor Max. PARP-10 is localized to the nuclear and cytoplasmic compartments that is controlled at least in part by a Leu-rich nuclear export sequence (NES). Functionally, PARP-10 inhibits c-Myc- and E1A-mediated cotransformation of rat embryo fibroblasts, a function that is independent of PARP activity but that depends on a functional NES. Together, our findings define a novel PARP enzyme involved in the control of cell proliferation.
authors.affiliation: Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH, Pauwelsstrasse 30, 52057 Aachen, Germany.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Sabine
authors.initials: S
authors.lastname: Schreek
authors.forename: Christa
authors.initials: C
authors.lastname: Cerni
authors.forename: Chantal
authors.initials: C
authors.lastname: Schamberger
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lesniewicz
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Poreba
authors.forename: Jörg
authors.initials: J
authors.lastname: Vervoorts
authors.forename: Gesa
authors.initials: G
authors.lastname: Walsemann
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Mehraein
authors.forename: Jürgen
authors.initials: J
authors.lastname: Mertsching
authors.forename: Regine
authors.initials: R
authors.lastname: Kraft
authors.forename: Matthias
authors.initials: M
authors.lastname: Austen
authors.forename: Juliane
authors.initials: J
authors.lastname: Lüscher-Firzlaff
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
mesh_terms: D000595:Amino Acid Sequence; D002455:Cell Division; D002460:Cell Line; D002874:Chromosome Mapping; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D010957:Plasmids; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism*; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C499627:PARP10 protein, human; D011065:Poly(ADP-ribose) Polymerases