Functional Interaction of CREB Binding Protein (CBP) with Nuclear Transport Proteins and Modulation by HDAC Inhibitors
| Autor: | Karin B. Kindle, David M. Heery, Janet C. Harries, Colm M. Ryan, Hilary M. Collins |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
alpha Karyopherins
Macromolecular Substances Nuclear Envelope Amino Acid Motifs Active Transport Cell Nucleus Importin Biology environment and public health Histone Deacetylases chemistry.chemical_compound Chlorocebus aethiops Animals Humans Enzyme Inhibitors Nuclear protein CREB-binding protein Molecular Biology Cell Nucleus Nuclear Proteins Alpha Karyopherins Sodium butyrate Cell Biology Histone acetyltransferase CREB-Binding Protein Protein Structure Tertiary Histone Deacetylase Inhibitors Nuclear Pore Complex Proteins Nuclear receptor coactivator 1 Crk-Associated Substrate Protein Biochemistry chemistry COS Cells biology.protein Nuclear transport Carrier Proteins Developmental Biology |
| Zdroj: | Cell Cycle. 5:2146-2152 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.5.18.3207 |
| Popis: | Nuclear transport proteins such as CSE1, NUP93 and Importin-alpha have recently been shown to be chromatin-associated proteins in yeast, which have unexpected functions in gene regulation. Here we report interactions between the mammalian histone acetyltransferase CBP with nuclear transport proteins CAS (a CSE1 homologue) and Importin-alpha (Impalpha) and NUP93. CAS was found to bind the SRC1 interaction domain (SID) of CBP via a leucine-rich motif in the N-terminus of the protein, that is conserved in other SID-binding proteins. Coimmunoprecipitation experiments also revealed that CBP and Impalpha proteins form a complex. As Impalpha is a known acetylation target of CBP/p300, and is recycled to the cytoplasm via the exportin CAS, we investigated whether HDAC inhibitors would alter the subcellular localization of these proteins. Treatment of COS-1 cells with the HDAC inhibitors trichostatin A or sodium butyrate resulted in sequestration of Impalpha in the nuclear envelope, accumulation of CAS in nuclear aggregates, and an increased number of CBP-containing PML bodies per cell. In addition, HDACi treatment appeared to enhance the association of Impalpha and CBP in coimmunoprecipitation experiments. Our results provide evidence for novel functional interactions between the chromatin modification enzyme CBP and nuclear transport proteins in mammalian cells. |
| Databáze: | OpenAIRE |
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