Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Collas, Philippe, Le Guellec, Katherine, Taskén, Kjetil
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168084/
https://www.ncbi.nlm.nih.gov/pubmed/10601332
_version_ 1782144841550921728
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
work_keys_str_mv AT collasphilippe theakinaseanchoringproteinakap95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis
AT leguelleckatherine theakinaseanchoringproteinakap95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis
AT taskenkjetil theakinaseanchoringproteinakap95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis
AT collasphilippe akinaseanchoringproteinakap95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis
AT leguelleckatherine akinaseanchoringproteinakap95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis
AT taskenkjetil akinaseanchoringproteinakap95isamultivalentproteinwithakeyroleinchromatincondensationatmitosis