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PMID:17172643
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 |
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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 |
edit table |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
enables |
GO:0033558: protein lysine deacetylase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
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 | |
enables |
GO:0033558: protein lysine deacetylase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
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 | |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O43809 |
F |
Seeded From UniProt |
complete | ||
involved_in |
GO:0016575: histone deacetylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
enables |
GO:0033558: protein deacetylase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
involved_in |
GO:0006476: protein deacetylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0016575: histone deacetylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
enables |
GO:0033558: protein deacetylase activity |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
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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