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PMID:19710015

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Citation

Crawford, NP, Yang, H, Mattaini, KR and Hunter, KW (2009) The metastasis efficiency modifier ribosomal RNA processing 1 homolog B (RRP1B) is a chromatin-associated factor. J. Biol. Chem. 284:28660-73

Abstract

There is accumulating evidence for a role of germ line variation in breast cancer metastasis. We have recently identified a novel metastasis susceptibility gene, Rrp1b (ribosomal RNA processing 1 homolog B). Overexpression of Rrp1b in a mouse mammary tumor cell line induces a gene expression signature that predicts survival in breast cancer. Here we extend the analysis of RRP1B function by demonstrating that the Rrp1b activation gene expression signature accurately predicted the outcome in three of four publicly available breast carcinoma gene expression data sets. In addition, we provide insights into the mechanism of RRP1B. Tandem affinity purification demonstrated that RRP1B physically interacts with many nucleosome binding factors, including histone H1X, poly(ADP-ribose) polymerase 1, TRIM28 (tripartite motif-containing 28), and CSDA (cold shock domain protein A). Co-immunofluorescence and co-immunoprecipitation confirmed these interactions and also interactions with heterochromatin protein-1alpha and acetyl-histone H4 lysine 5. Finally, we investigated the effects of ectopic expression of an RRP1B allelic variant previously associated with improved survival in breast cancer. Gene expression analyses demonstrate that, compared with ectopic expression of wild type RRP1B in HeLa cells, the variant RRP1B differentially modulates various transcription factors controlled by TRIM28 and CSDA. These data suggest that RRP1B, a tumor progression and metastasis susceptibility candidate gene, is potentially a dynamic modulator of transcription and chromatin structure.

Links

PubMed PMC2781410 Online version:10.1074/jbc.M109.023457

Keywords

Amino Acid Motifs; Animals; Cell Nucleus/metabolism; Chromatin/chemistry; Chromosomal Proteins, Non-Histone/metabolism; Chromosomal Proteins, Non-Histone/physiology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Mice; Mitosis; Neoplasm Metastasis; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; Polymorphism, Genetic; RNA, Ribosomal/metabolism; Repressor Proteins/metabolism

Significance

Annotations

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

MOUSE:NUCL

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91YK2

F

Seeded From UniProt

complete

HUMAN:PARP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14684-1

F

Seeded From UniProt

complete

MOUSE:PARP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91YK2

F

Seeded From UniProt

complete

HUMAN:H4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14684-1

F

Seeded From UniProt

complete

HUMAN:H4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P09874

F

Seeded From UniProt

complete

HUMAN:H4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P62805

F

Seeded From UniProt

complete

MOUSE:NPM

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91YK2

F

Seeded From UniProt

complete

MOUSE:TIF1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91YK2

F

Seeded From UniProt

complete

MOUSE:Q80ZM5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91YK2

F

Seeded From UniProt

complete

MOUSE:RRP1B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

MGI:MGI:1340806
MGI:MGI:2685307
PR:P09405
PR:Q61937
PR:Q62318
PR:Q9JKB3

F

Seeded From UniProt

complete

MOUSE:RRP1B

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RRP1B

located_in

GO:0000791: euchromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RRP1B

located_in

GO:0000792: heterochromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:YBOX3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q91YK2

F

Seeded From UniProt

complete


See also

References

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