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...
Autores principales: | , , |
---|---|
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 |
Sumario: | 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. |
---|