Disease relevance of ABI2

• Functions of early (AP-2) and late (AIP1/ALIX) endocytic proteins in equine infectious anemia virus budding [1].
• The genetic variability within PT/SAP, LYP and LXXLF HIV-1 P6gag motifs, required for the binding to Tsg101 and AIP1 cellular host proteins during viral budding, was examined in 122 HIV-infected subjects [2].
• AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding [3].
• Rapid actin monomer-insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1 [4].
• BACKGROUND: Abelson (Abl) interactor 2 (Abi-2) has been considered as a key regulator of cell/tissue structural organization and is differentially expressed in leiomyomas [5].

High impact information on ABI2

• Abi-2 is a novel protein that contains an SH3 domain and proline-rich sequences critical for binding to c-Abl [6].
• We show that Abi-2 is a substrate for the c-Abl tyrosine kinase [6].
• The cooperative activities of cofilin, coronin, and Aip1 should provide a biochemical basis for understanding how actin filaments can grow in some places in the cell while shrinking in others [4].
• By biochemical fractionation, we identify Aip1 and coronin as two proteins present in thymus extract that facilitate the cofilin-mediated disassembly of Listeria comet tails [4].
• Thus, ABI1 and ABI2 seem to control fibrillin expression that is involved in mediating ABA-induced photoprotection [7].

Biological context of ABI2

• ABI2-deficient mice exhibit defective cell migration, aberrant dendritic spine morphogenesis, and deficits in learning and memory [8].
• Homozygous deletion of murine abi2 produced abnormal phenotypes in the eye and brain, the tissues with the highest Abi2 expression [8].
• The characterisation of type 2C protein phosphatases, ABI1 and ABI2, implicates negative control and redundant action on the signal pathway of this hormone [9].
• Expression of an Abi-2 mutant protein that lacks sequences required for binding to the Abl SH3 domain but retains binding to the Abl carboxyl terminus activates the transforming capacity of c-Abl [6].
• ArgBP1 contains a C-terminal SH3 domain, several PEST sequences, a serine rich domain and an SH3 binding site [10].

Anatomical context of ABI2

• The association of ArgBP1 with Arg in living cells was confirmed by coimmunoprecipitation in cotransfected COS cells [10].
• ArgBP1 is ubiquitously expressed as two transcripts of approximately 2.2 kb and approximately 8 kb with highest levels in brain, heart and testis [10].
• These findings support a role for Abi2 in the regulation of cytoskeletal dynamics at adherens junctions and dendritic spines, which is critical for intercellular connectivity, cell morphogenesis, and cognitive functions [8].
• Endogenous SETA and AIP1 proteins showed similar patterns of staining in primary rat astrocytes [11].
• The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-beta [5].

Associations of ABI2 with chemical compounds

• Analysis of the mechanism of association indicated that the ArgBP1 SH3 domain binds to a C-terminal Arg SH3-binding site, and that an N-terminal ArgBP1 proline-rich sequence binds to the Arg SH3 domain [10].
• The drug regimens consisted of single dose of albendazole 400 mg (A1, n=34), 3 days of albendazole 400 mg daily (A3, n=34), 5 days of albendazole 400 mg daily (A5, n=35), single dose of albendazole 400 mg plus praziquantel 40 mg/kg (AIP1, n=34), and 3 days of albendazole 400 mg plus praziquantel 40 mg/kg daily (A3P3, n=36) [12].

Other interactions of ABI2

• In search of a function for the E3B1/Abi2/Argbp1/NESH family (Review) [13].
• An E3B1/Abi2/Argbp1/NESH protein family has recently emerged from analysis of the sequence and structural similarities [13].
• In line with the mutational analysis, overexpression of dominant negative (DN) mutants and wild-type TSG101 but not the DN mutant of AIP-1/ALIX reduced PFV particle release and infectivity [14].
• ArgBP1 may be the key protein, which accounts for the physiological function of ADAM19 [15].
• The similarity of the ArgBP1 expression pattern and subcellular localization to those of Arg and the potential for a highly specific and potentially strong association mediated by two pairs of SH3 domain/proline-rich motif interactions, suggest that ArgBP1 is likely to be a regulator and/or effector of Arg function [10].

Analytical, diagnostic and therapeutic context of ABI2

• In co-immunoprecipitation experiments, SETA and AIP1 interacted and could form a complex with apoptosis-linked gene 2 protein [11].
• Site-directed mutagenesis suggested that Aip1p has two actin binding sites, the primary actin binding site lies on the edge of its N-terminal beta-propeller and a secondary actin binding site lies in a comparable location on its C-terminal beta-propeller [16].
• A genetic dissection of Aip1p's interactions leads to a model for Aip1p-cofilin cooperative activities [16].
• Western blotting showed a similar trend in Abi-2 protein expression in leiomyoma/myometrial tissue extracts, which was immunolocalized in LSMC and MSMC, connective tissue fibroblasts and arterial walls [5].

References