Disease relevance of AKAP8L

• Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses [1].
• Overexpression of HAP95 significantly increases CTE-dependent gene expression but has no effect on general gene expression or that mediated by the Rev/Rev response element of human immunodeficiency virus type 1 [2].
• Protein kinase A associates with HA95 and affects transcriptional coactivation by Epstein-Barr virus nuclear proteins [3].

High impact information on AKAP8L

• HDAC3 forms a complex with A-Kinase-Anchoring Proteins AKAP95 and HA95, which are targeted to mitotic chromosomes [4].
• HA95-LAP2 beta interaction is not required for NE formation [5].
• A second domain sufficient to bind HA95 colocalizes with the lamin B-binding domain of LAP2beta at residues 299-373 [5].
• HA95 is a chromatin-associated protein that interfaces the nuclear envelope (NE) and chromatin [5].
• We propose that an interaction of LAP2beta, or LAP2 proteins, with HA95 is involved in the control of initiation of DNA replication [5].

Biological context of AKAP8L

• In contrast, immunoblocking of HA95 bound to condensed chromosomes does not impair chromatin decondensation, nuclear membrane reassembly or lamina reformation [6].
• Our results argue for a role for HA95 in anchoring nuclear membranes and lamins to chromatin in interphase, and in releasing membranes from chromatin at mitosis [6].
• Biochemical and photobleaching data indicate that HA95 is tightly associated with chromatin and the nuclear matrix/lamina network in interphase, and bound to chromatin at mitosis [6].
• We propose that HA95 is a central platform at the chromatin/nuclear matrix interface implicated in regulating nuclear envelope-chromatin interactions during the cell cycle [6].
• We report an interaction between HA95 and the inner nuclear membrane protein lamina-associated polypeptide (LAP) 2 beta, and a role of this association in initiation of DNA replication [5].

Anatomical context of AKAP8L

• The data also suggest that HA95 is not involved in initial binding of membranes to chromatin upon nuclear reassembly [6].
• Intra-nuclear blocking of HA95 with anti-HA95 antibodies abolishes nuclear breakdown in a mitotic HeLa cell extract [6].

Physical interactions of AKAP8L

• Taken together, these data support the proposal that HAP95 specifically facilitates CTE-mediated gene expression by directly binding to RHA [1].

Co-localisations of AKAP8L

• In interphase, HA95 is co-localized with AKAP95, but the two proteins are not biochemically associated [7].

Regulatory relationships of AKAP8L

• Inhibition of PKC, MAP kinase, or CaM kinase II does not affect mitotic extract-induced dissociation of LAP2beta from HA95 [8].

Other interactions of AKAP8L

• Cross-linking experiments, however, illustrate a tight association of HA95 with LBR and LAP2 only [6].
• We report a role for HA95, a nuclear protein with high homology to the nuclear A-kinase anchoring protein AKAP95, in the regulation of nuclear envelope-chromatin interactions [6].
• Finally, we showed that HAP95 synergizes significantly with RHA on CTE-mediated reporter gene expression and promotes nuclear export of unspliced mRNA in transfected cells [1].
• Identification, cloning and characterization of a novel nuclear protein, HA95, homologous to A-kinase anchoring protein 95 [7].

References