Insights into key kinase regulatory network of LARP1 based on co-occurring phosphorylation events

LARP1 (La-related protein 1) is an important mediator of translation regulation that stabilizes terminal oligopyrimidine motif-containing mRNAs. LARP1, being a direct target of mechanistic Target of Rapamycin Complex 1 (mTORC1), undergoes phosphorylation in the presence of growth factors. Phosphorylation-dependent conformational changes in LARP1 dictate its ability to stabilize or repress mRNAs with 5' terminal oligopyrimidine (TOP), which code for key proteins in ribosome biogenesis and translation. Due to this important role, LARP1 is involved in cancer cell survival, facilitating selective translation of oncogenic proteins with a tradeoff in cap-dependent translation. As the function of LARP1 is governed by phosphorylation, this review provides phosphoproteomics-based regulatory network of LARP1, identifying major phosphorylation sites, upstream kinases, and interactors, with mutual co-differential regulation events. Extensive literature synthesis identified 11 major phosphorylation sites of LARP1, and an understanding of interaction dynamics that contribute to functional plasticity of LARP1. Specially, this article synthesizes the co-regulatory network of LARP1 with other proteins, and the interactions central to mTOR signaling, phosphorylation of LARP1, and its functional role in disease manifestation. This approach focusing on the LARP1-kinase regulatory network is crucial in untangling its miscellaneous role in cancer, which provides novel therapeutic paths for malignancies.