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The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis
Protein kinase A (PKA) and the nuclear A-kinase–anchoring protein AKAP95 have previously been shown to localize in separate compartments in interphase but associate at mitosis. We demonstrate here a role for the mitotic AKAP95–PKA complex. In HeLa cells, AKAP95 is associated with the nuclear matrix...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1999
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168084/ https://www.ncbi.nlm.nih.gov/pubmed/10601332 |
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author | Collas, Philippe Le Guellec, Katherine Taskén, Kjetil |
author_facet | Collas, Philippe Le Guellec, Katherine Taskén, Kjetil |
author_sort | Collas, Philippe |
collection | PubMed |
description | Protein kinase A (PKA) and the nuclear A-kinase–anchoring protein AKAP95 have previously been shown to localize in separate compartments in interphase but associate at mitosis. We demonstrate here a role for the mitotic AKAP95–PKA complex. In HeLa cells, AKAP95 is associated with the nuclear matrix in interphase and redistributes mostly into a chromatin fraction at mitosis. In a cytosolic extract derived from mitotic cells, AKAP95 recruits the RIIα regulatory subunit of PKA onto chromatin. Intranuclear immunoblocking of AKAP95 inhibits chromosome condensation at mitosis and in mitotic extract in a PKA-independent manner. Immunodepletion of AKAP95 from the extract or immunoblocking of AKAP95 at metaphase induces premature chromatin decondensation. Condensation is restored in vitro by a recombinant AKAP95 fragment comprising the 306–carboxy-terminal amino acids of the protein. Maintenance of condensed chromatin requires PKA binding to chromatin-associated AKAP95 and cAMP signaling through PKA. Chromatin-associated AKAP95 interacts with Eg7, the human homologue of Xenopus pEg7, a component of the 13S condensin complex. Moreover, immunoblocking nuclear AKAP95 inhibits the recruitment of Eg7 to chromatin in vitro. We propose that AKAP95 is a multivalent molecule that in addition to anchoring a cAMP/PKA–signaling complex onto chromosomes, plays a role in regulating chromosome structure at mitosis. |
format | Text |
id | pubmed-2168084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21680842008-05-01 The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis Collas, Philippe Le Guellec, Katherine Taskén, Kjetil J Cell Biol Original Article Protein kinase A (PKA) and the nuclear A-kinase–anchoring protein AKAP95 have previously been shown to localize in separate compartments in interphase but associate at mitosis. We demonstrate here a role for the mitotic AKAP95–PKA complex. In HeLa cells, AKAP95 is associated with the nuclear matrix in interphase and redistributes mostly into a chromatin fraction at mitosis. In a cytosolic extract derived from mitotic cells, AKAP95 recruits the RIIα regulatory subunit of PKA onto chromatin. Intranuclear immunoblocking of AKAP95 inhibits chromosome condensation at mitosis and in mitotic extract in a PKA-independent manner. Immunodepletion of AKAP95 from the extract or immunoblocking of AKAP95 at metaphase induces premature chromatin decondensation. Condensation is restored in vitro by a recombinant AKAP95 fragment comprising the 306–carboxy-terminal amino acids of the protein. Maintenance of condensed chromatin requires PKA binding to chromatin-associated AKAP95 and cAMP signaling through PKA. Chromatin-associated AKAP95 interacts with Eg7, the human homologue of Xenopus pEg7, a component of the 13S condensin complex. Moreover, immunoblocking nuclear AKAP95 inhibits the recruitment of Eg7 to chromatin in vitro. We propose that AKAP95 is a multivalent molecule that in addition to anchoring a cAMP/PKA–signaling complex onto chromosomes, plays a role in regulating chromosome structure at mitosis. The Rockefeller University Press 1999-12-13 /pmc/articles/PMC2168084/ /pubmed/10601332 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Collas, Philippe Le Guellec, Katherine Taskén, Kjetil The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis |
title | The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis |
title_full | The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis |
title_fullStr | The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis |
title_full_unstemmed | The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis |
title_short | The a-Kinase–Anchoring Protein Akap95 Is a Multivalent Protein with a Key Role in Chromatin Condensation at Mitosis |
title_sort | a-kinase–anchoring protein akap95 is a multivalent protein with a key role in chromatin condensation at mitosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168084/ https://www.ncbi.nlm.nih.gov/pubmed/10601332 |
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