High impact information on Abi1

• We suggest that the Abi-1 protein may serve as a regulator of Abl function in transformation or in signal transduction [1].
• A novel cellular protein, Abl-interactor-1 (Abi-1), which specifically interacts with the carboxy-terminal region of Abl oncoproteins, has been identified in a mouse leukemia cell line [1].
• Conversely, full-length Eps8 is auto-inhibited in vitro, and interaction with the Abi1 protein relieves this inhibition [2].
• Sra-1 and Nap1 link Rac to actin assembly driving lamellipodia formation [3].
• Thus, Abi-1 undergoes nucleocytoplasmic shuttling and functions at the leading edge to regulate Wave-1 localization and protein levels [4].

Biological context of Abi1

• Moreover, removal of Sra-1 or Nap1 by RNA interference abrogated the formation of Rac-dependent lamellipodia induced by growth factor stimulation or aluminium fluoride treatment [3].
• Reducing the levels of WAVE2, directly or by targeting Abi1, resulted in an impaired cell migration to CSF-1 [5].
• Abl-interactor-1, a novel SH3 protein binding to the carboxy-terminal portion of the Abl protein, suppresses v-abl transforming activity [1].
• Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching [6].
• A striking phenotype seen in approximately one quarter of Nap1 mutants is the duplication of the anteroposterior body axis [6].

Anatomical context of Abi1

• Altogether these data identify a WAVE2-Abi1 complex crucial for the normal actin cytoskeleton reorganization and migration of macrophages in response to CSF-1 [5].
• Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of the Abelson interactor protein Abi-1 [7].
• The axis duplications arise because Nap1 is required for the normal polarization and migration of cells of the Anterior Visceral Endoderm (AVE), an early extraembryonic organizer tissue [6].
• Other morphogenetic processes appear to proceed normally in the absence of Nap1/WAVE activity: the notochord, the layers of the heart, and the epithelial-to-mesenchymal transition (EMT) at gastrulation appear normal [6].
• Here, we show that mouse embryos that lack Nap1, a regulatory component of the WAVE complex, arrest at midgestation and have defects in morphogenesis of all three embryonic germ layers [6].

Associations of Abi1 with chemical compounds

• Further, we demonstrated that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent manner and that complete nuclear translocation of Abi-1 in the absence of LMB requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1 [4].

Physical interactions of Abi1

• WAVE2 was found in a protein complex together with Abelson kinase interactor 1 (Abi1) in resting or stimulated cells [5].

Other interactions of Abi1

• Both WAVE2 and Abi1 were recruited to and necessary for the formation of F-actin protrusions in response to CSF-1 [5].

References