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PMID:15674325

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Citation

Yu, M, Schreek, S, Cerni, C, Schamberger, C, Lesniewicz, K, Poreba, E, Vervoorts, J, Walsemann, G, Grötzinger, J, Kremmer, E, Mehraein, Y, Mertsching, J, Kraft, R, Austen, M, Lüscher-Firzlaff, J and Lüscher, B (2005) PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene 24:1982-93

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.

Links

PubMed Online version:10.1038/sj.onc.1208410

Keywords

Amino Acid Sequence; Cell Division; Cell Line; Chromosome Mapping; Humans; In Situ Hybridization, Fluorescence; Molecular Sequence Data; Plasmids; Poly(ADP-ribose) Polymerases/genetics; Poly(ADP-ribose) Polymerases/metabolism; Protein Biosynthesis; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-myc/metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Transcription, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MYC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P19338

F

Seeded From UniProt

complete

HUMAN:MYC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q09472

F

Seeded From UniProt

complete

HUMAN:MYC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92793

F

Seeded From UniProt

complete

HUMAN:MYC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q53GL7

F

Seeded From UniProt

complete

HUMAN:PARP1

involved_in

GO:0070212: protein poly-ADP-ribosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:NUCL

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01106

F

Seeded From UniProt

complete

HUMAN:TYY1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01106

F

Seeded From UniProt

complete

HUMAN:MAX

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01106

F

Seeded From UniProt

complete

HUMAN:EP300

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01106

F

Seeded From UniProt

complete

HUMAN:PAR10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01106

F

Seeded From UniProt

complete

HUMAN:PAR10

involved_in

GO:0048147: negative regulation of fibroblast proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR10

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PAR10

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PAR10

involved_in

GO:0010847: regulation of chromatin assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PAR10

involved_in

GO:0070212: protein poly-ADP-ribosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CBP

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01106

F

Seeded From UniProt

complete

CHICK:PARP1

involved_in

GO:0070212: protein poly-ADP-ribosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

enables

GO:0070491: repressing transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P25490

F

Seeded From UniProt

complete

HUMAN:MYC

involved_in

GO:0048146: positive regulation of fibroblast proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:MYC

enables

GO:0008134: transcription factor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P61244

F

Seeded From UniProt

complete


See also

References

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