Disease relevance of ANP32A

• We had previously described the leucine-rich acidic nuclear protein (LANP) as a candidate mediator of toxicity in the polyglutamine disease, spinocerebellar ataxia type 1 (SCA1) [1].
• Adenovirus E4orf6 targets pp32/LANP to control the fate of ARE-containing mRNAs by perturbing the CRM1-dependent mechanism [2].
• Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells [3].
• Taken together, our results suggest that nucleolin, PHAP II, and PHAP I appear to be functional as potential receptors in the HIV binding process by virtue of their capacity to interact with the V3 loop of gp120 [4].
• The current investigation was designed to compare the beneficial effects of LANP and vessel dilator in persons with congestive heart failure (CHF) [5].
• The addition of recombinant pp32/putative human HLA class II-associated protein (pp32/PHAPI), described as a putative tumor suppressor in prostate cancer, successfully restored defective cytochrome c-induced caspase activation in vitro [6].

High impact information on ANP32A

• LANP is expressed predominantly in Purkinje cells, the primary site of pathology in SCA1 [7].
• GrnA-induced cytotoxicity and cleavage of PHAP II, a previously identified GrnA substrate, are unimpaired in Jurkat cells that overexpress bcl-2 [8].
• C-fos mRNA was exported together with E4orf6, E1B-55kD, pp32/LANP, and HuR proteins [2].
• Using this approach, we have also assessed the ability of putative apoptosome regulatory proteins, such as Smac/DIABLO and PHAPI, to regulate the activity of native apoptosomes [9].
• Mapmodulin inhibits the initial rate of MAP2 binding to microtubules, a property that may allow mapmodulin to displace MAPs from the path of organelles translocating along microtubules [10].

Biological context of ANP32A

• A similar heterocomplex, formed by SET (A and B) and ANP32A as major subunits, possess histone acetyltransferase inhibitory activity (INHAT), and have a role in chromatin remodeling and transcriptional regulation (histone code) [11].
• How phosphorylated Rb protects cells from apoptosis is not well understood, but there is evidence that Rb may sequester a pro-apoptotic nuclear factor. pp32 (ANP32A) is a pro-apoptotic nuclear phosphoprotein, the expression of which is commonly increased in cancer [12].
• The amino acid sequences of two tryptic peptides derived from purified preparations of I1PP2A indicated that this potent heat-stable protein inhibitor of protein phosphatase 2A (PP2A) may be equivalent to putative histocompatibility leukocyte antigens class II-associated protein I (PHAP-I) [13].
• Localization of the gene encoding the putative human HLA class II associated protein (PHAPI) to chromosome 15q22.3-q23 by fluorescence in situ hybridization [14].
• Normal human peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin-P (PHAP) and cyclosporine (CsA) to investigate the mode of action of CsA on cellular proliferation [15].

Anatomical context of ANP32A

• LANP thus could play a key role in neuronal development and/or neurodegeneration by its interactions with microtubule associated proteins [1].
• Here we report on two putative HLA class II associated proteins (PHAPI and PHAPII) which have been purified from the cytosolic fraction of the human lymphoblastoid B-cell line H2LCL using an affinity matrix composed of the synthetic biotinylated cytoplasmic region of the DR2 alpha chain immobilized on avidin agarose [16].
• PHAP II begins to be degraded within minutes of initiation of cytotoxic T lymphocyte attack [17].
• In support of this possibility, mapmodulin stimulates the microtubule- and dynein-dependent localization of Golgi complexes in semi-intact CHO cells [10].
• Overexpression of GFP-I1PP2A/lanp in PC12 cells leads to markedly reduced neurite length on laminin 5 after induction with nerve growth factor [18].

Associations of ANP32A with chemical compounds

• The sequence obtained for PHAPI revealed a novel primary structure with a leucine/isoleucine rich N-terminal region [16].
• Herein we describe the characteristic features of the Anp32 family represented by the cerebellar leucine-rich repeat protein (Lanp) and the cerebellar developmental-regulated protein 1 (Cpd1) [19].
• The phosphatase binds to the cytoplasmic membrane-proximal conserved GFFKR motif of the alpha integrin subunit, whereas I1PP2A/lanp requires a longer sequence for binding [18].
• Filler treatment with small amounts of MAPM shifted the alpha-relaxations to higher temperatures; they were shifted back to lower temperatures when the filler was treated with large amounts of silane [20].
• 3-Acryloxypropyltrimethoxysilane (MAPM) and 4-aminobutyltriethoxysilane (ABTE) were used as silanating coupling agents [20].

Other interactions of ANP32A

• Further experiments revealed that silencing of ANP32A and ANP32B inhibited AAV replication, while overexpression of all of the components of the TAF-I/Set complex increased de novo AAV DNA synthesis in permissive cells [21].
• Both PHAPI and PHAPII have an extended highly acidic C-terminal region [16].
• We have purified and characterized a 31-kDa protein named mapmodulin that binds to the microtubule-associated proteins (MAPs) MAP2, MAP4, and tau [10].
• PHAP II, a substrate of granzyme A, is degraded within minutes of CTL attack [22].

Analytical, diagnostic and therapeutic context of ANP32A

• Immunofluorescence studies demonstrate that both LANP and ataxin-1 colocalize in nuclear matrix-associated subnuclear structures [7].
• Using affinity chromatography with recombinant mutant inactive granzyme A, we previously isolated two granzyme A-binding proteins, PHAP (putative HLA-associated protein) I and II [22].
• Aided performance was represented by the Profile of Hearing Aid Performance (PHAP, Cox & Gilmore, 1990) [23].
• These requirements were met by exposure of cell cultures to: (1) PHAE, the erythroagglutinating component of PHAP, or (2) to either non-erythroagglutinating mitogens, PHAL, Con A, OKT3 or SEA, or to antigens of typhus group rickettsiae or salmonellae, provided that the RBC membrane was desialyted [24].

References