Multisynthetase complex auxiliary component p38 (AIMP2)

Multisynthetase complex auxiliary component p38 (AIMP2) is a non-enzymatic scaffolding protein required for the assembly and stability of the multi-aminoacyl-tRNA synthetase complex, a critical cellular machinery involved in the first step of protein synthesis[1][5][6]. While its primary function is to help organize the tRNA synthetases, AIMP2 exerts significant regulatory roles in cell biology. Upon cellular stress or DNA damage, AIMP2 can dissociate from the complex and translocate to the nucleus, where it stabilizes the tumor suppressor p53 by preventing its degradation, thereby promoting apoptosis and acting as a tumor suppressor[3][4]. AIMP2 also facilitates the ubiquitin-mediated degradation of FUBP1, thereby downregulating MYC and limiting cell proliferation[5]. Alternative splicing leading to the AIMP2-DX2 variant diminishes p53-mediated tumor suppression and is implicated in several cancers and chemoresistance[4][7]. In the nervous system, accumulation of AIMP2 due to Parkin dysfunction contributes to neurodegeneration in Parkinson’s disease[4]. No direct drugs currently target AIMP2, but its biological pathways intersect with important therapeutic axes such as the p53-MDM2 pathway and MYC regulation[3][5]. The splice variant AIMP2-DX2/full-length AIMP2 ratio is considered an emerging biomarker in certain malignancies[4][7]. Safety concerns for experimental targeting involve the molecule’s essential cellular functions and broad consequences of altering protein synthesis or cell survival pathways.

Other names

Aminoacyl tRNA synthetase complex-interacting multifunctional protein 2JTV1JTV-1p38PRO0992HLD17ARS-interacting multifunctional protein 2Protein JTV-1multisynthase complex auxiliary component p38multisynthetase complex auxiliary component p38

Not generally targeted by drugs directly, but agents modulating p53-MDM2 interaction (like Nutlin-3) can compensate for AIMP2 loss[3]. Splice-switching oligonucleotides or related approaches could, in principle, target pathological splicing variants such as AIMP2-DX2[4][7].