PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation.
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.
Yu
Mei
M
Abteilung Biochemie und Molekularbiologie, Institut für Biochemie, Klinikum der RWTH, Pauwelsstrasse 30, 52057 Aachen, Germany.
Schreek
Sabine
S
Cerni
Christa
C
Schamberger
Chantal
C
Lesniewicz
Krzysztof
K
Poreba
Elzbieta
E
Vervoorts
Jörg
J
Walsemann
Gesa
G
Grötzinger
Joachim
J
Kremmer
Elisabeth
E
Mehraein
Yasmin
Y
Mertsching
Jürgen
J
Kraft
Regine
R
Austen
Matthias
M
Lüscher-Firzlaff
Juliane
J
Lüscher
Bernhard
B
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
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C499627:PARP10 protein, human; D011065:Poly(ADP-ribose) Polymerases