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. 2020 Nov 27;8:599765. doi: 10.3389/fcell.2020.599765

FIGURE 3.

FIGURE 3

Roles of AIMP2 and AIMP2-DX2 in the development of lung cancer. AIMP2 dissociates from the MSC and translocates to the nucleus. The nuclear AIMP2 interacts with Smurf2, thereby enhancing FBP ubiquitination and down-regulating c-Myc. Meanwhile, the interaction also inhibits the binding of Smurf2 to CRM1, which enhances TGF-β signal by reducing the nuclear output of Smurf2. HSP70 inhibits the Siah1-dependent AIMP2-DX2 ubiquitination by interacting with AIMP2-DX2, thereby maintaining the stabilization of AIMP2-DX2. AIMP2-DX2 inhibits p14/ARF by directly binding to it, thereby suppressing oncogene-induced apoptosis and senescence. AIMP2, ARS-interacting multifunctional protein 2; AIMP2-DX2, AIMP2 lacking exon 2; MSC, multi-tRNA synthetase complex; MAPK, mitogen-activated protein kinase; Smurf2, Smad ubiquitin regulatory factors 2; FBP, FUSE-binding protein; CRM1, chromosomal region maintenance 1; TGF-β, transforming growth factor-β; HSP70, heat shock protein 70; Siah1, Seven in absentia homolog 1.