A-kinase anchor protein 8

Definition:

Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring. May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression. Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L. Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation. May be involved in regulation of DNA replication by acting as scaffold for MCM2. Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation. May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells. May act as a carrier protein of GJA1 for its transport to the nucleus. May play a repressive role in the regulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and transcribed regions. Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (By similarity).

References:

[1]. Anne Marstad, et al. A-kinase anchoring protein AKAP95 is a novel regulator of ribosomal RNA synthesis. FEBS J. 2016 Feb;283(4):757-70. [Content Brief]

[2]. Tatjana Arsenijevic, et al. A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95. Biochem J. 2004 Mar 1;378(Pt 2):673-9. [Content Brief]

[3]. Hao Jiang, et al. Regulation of transcription by the MLL2 complex and MLL complex-associated AKAP95. Nat Struct Mol Biol. 2013 Oct;20(10):1156-63. [Content Brief]

[4]. Yun Li, et al. A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity. Genes Dev. 2006 Sep 15;20(18):2566-79. [Content Brief]

[5]. Turid Eide, et al. Protein kinase A-anchoring protein AKAP95 interacts with MCM2, a regulator of DNA replication. J Biol Chem. 2003 Jul 18;278(29):26750-6. [Content Brief]

[6]. Xiaoxuan Chen, et al. Dynamic changes in protein interaction between AKAP95 and Cx43 during cell cycle progression of A549 cells. Sci Rep. 2016 Feb 16;6:21224. [Content Brief]

[7]. Turid Eide, et al. Distinct but overlapping domains of AKAP95 are implicated in chromosome condensation and condensin targeting. EMBO Rep. 2002 May;3(5):426-32. [Content Brief]

[8]. Xianlong Gao, et al. Localization and retention of p90 ribosomal S6 kinase 1 in the nucleus: implications for its function. Mol Biol Cell. 2012 Feb;23(3):503-15. [Content Brief]

[9]. P Collas, et al. The A-kinase-anchoring protein AKAP95 is a multivalent protein with a key role in chromatin condensation at mitosis. J Cell Biol. 1999 Dec 13;147(6):1167-80. [Content Brief]

[10]. T Eide, et al. Molecular cloning, chromosomal localization, and cell cycle-dependent subcellular distribution of the A-kinase anchoring protein, AKAP95. Exp Cell Res. 1998 Feb 1;238(2):305-16. [Content Brief]

[11]. R L Steen, et al. A kinase-anchoring protein (AKAP)95 recruits human chromosome-associated protein (hCAP)-D2/Eg7 for chromosome condensation in mitotic extract. J Cell Biol. 2000 May 1;149(3):531-6. [Content Brief]

[12]. Shinji Kamada, et al. A-kinase-anchoring protein 95 functions as a potential carrier for the nuclear translocation of active caspase 3 through an enzyme-substrate-like association. Mol Cell Biol. 2005 Nov;25(21):9469-77. [Content Brief]

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