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PMID:17172643

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Citation

Shimazu, T, Horinouchi, S and Yoshida, M (2007) Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'-end processing. J. Biol. Chem. 282:4470-8

Abstract

Trichostatin A (TSA), a specific inhibitor of histone deacetylases (HDACs), induces acetylation of various non-histone proteins such as p53 and alpha-tubulin. We purified several acetylated proteins by the affinity to an anti-acetylated lysine (AcLys) antibody from cells treated with TSA and identified them by mass spectrometry. Here we report on acetylation of CFIm25, a component of mammalian cleavage factor Im (CF Im), and poly(A) polymerase (PAP), a polyadenylating enzyme for the pre-mRNA 3'-end. The residues acetylated in these proteins were mapped onto the regions required for interaction with each other. Whereas CBP acetylated these proteins, HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2 were involved in in vivo deacetylation. Acetylation of the CFIm25 occurred depending on the cleavage factor complex formation. Importantly, the interaction between PAP and CF Im complex was decreased by acetylation. We also demonstrated that acetylation of PAP inhibited the nuclear localization of PAP by inhibiting the binding to the importin alpha/beta complex. These results suggest that CBP and HDACs regulate the 3'-end processing machinery and modulate the localization of PAP through the acetylation and deacetylation cycle.

Links

PubMed Online version:10.1074/jbc.M609745200

Keywords

3' Untranslated Regions/metabolism; Acetylation/drug effects; Animals; COS Cells; CREB-Binding Protein/metabolism; Cercopithecus aethiops; Enzyme Inhibitors/pharmacology; Histone Deacetylase Inhibitors; Histone Deacetylases/metabolism; Humans; Hydroxamic Acids/pharmacology; Polynucleotide Adenylyltransferase/metabolism; Protein Binding/drug effects; Protein Processing, Post-Translational/drug effects; RNA Precursors/metabolism; RNA Processing, Post-Transcriptional/drug effects; RNA Processing, Post-Transcriptional/physiology; Sirtuin 1; Sirtuin 2; Sirtuins/metabolism; Tubulin/metabolism; Tumor Suppressor Protein p53/metabolism; alpha Karyopherins/metabolism; beta Karyopherins; mRNA Cleavage and Polyadenylation Factors/metabolism

Significance

Annotations

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

HUMAN:HDAC3

enables

GO:0033558: protein lysine deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HDAC3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43809

F

Seeded From UniProt

complete

HUMAN:CPSF5

enables

GO:0042826: histone deacetylase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q969S8

F

Seeded From UniProt

complete

HUMAN:CPSF5

enables

GO:0042826: histone deacetylase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O15379

F

Seeded From UniProt

complete

HUMAN:CPSF5

enables

GO:0042826: histone deacetylase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13547

F

Seeded From UniProt

complete

HUMAN:CPSF5

enables

GO:0042826: histone deacetylase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8IXJ6

F

Seeded From UniProt

complete

HUMAN:CPSF5

enables

GO:0042826: histone deacetylase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96EB6

F

Seeded From UniProt

complete

HUMAN:HDAC1

enables

GO:0033558: protein lysine deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HDAC1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43809

F

Seeded From UniProt

complete

HUMAN:SIR2

involved_in

GO:0006476: protein deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SIR2

enables

GO:0033558: protein lysine deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SIR2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43809

F

Seeded From UniProt

complete

HUMAN:HDA10

involved_in

GO:0006476: protein deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HDA10

enables

GO:0033558: protein lysine deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HDA10

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43809

F

Seeded From UniProt

complete

HUMAN:SIR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43809

F

Seeded From UniProt

complete

HUMAN:SIRT1

involved_in

GO:0016575: histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HDAC3

enables

GO:0033558: protein deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HDAC3

involved_in

GO:0006476: protein deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SIR1

involved_in

GO:0016575: histone deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HDAC1

enables

GO:0033558: protein deacetylase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HDAC1

involved_in

GO:0006476: protein deacetylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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