Biochemical Feature of LMO2 Interactome and LMO2 Function Prospect

Abstract

Background LMO2 belongs to the LIM-Only group of LIM domain protein superfamily. It is ubiquitously expressed in different types of tissues and locates either in the nucleus or in the cytoplasm depending on the tissue type. Till now the unique function of LMO2 was considered to be serving as a bridging or blocking molecule that mediates extensive protein-protein interactions. However, the exactly biological features of LMO2 interactome as well as LMO2 function spectrum remain largely unclear. Material/Methods In this study, yeast 2-hybrid assay was firstly performed using LMO2 as the bait and the characteristic of LMO2 protein interactome was analyzed according to the yeast 2-hybrid data and other relative biological information primarily using bioinformatic method. Results Our data indicated that LMO2 favored interacting with peptides containing β-sheet structure and having relatively unstable confirmation. Moreover, several LMO2 favored interacting domains were identified, including WD40 repeat, coiled-coil, Ankyrin repeat, Zinc finger, PDZ, and SH3, and functions of these domain-containing members were dramatically enriched in some types of cancers. Conclusions Our results revealed a LMO2 favored protein-interaction pattern in both secondary structure and domain level, and concentrated LMO2 function in kinds of cytoplasmic metabolism pathways as well as multiple types of cancers.

LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1

“…It has been reported that LMO2 played a carcinogenic role in prostate cancer and glioblastoma [ 28 , 29 ], and yet is a good prognostic marker for diffuse large B-cell lymphoma and pancreatic cancer [ 30 , 31 ]. These opposite functions may be due to the fact that LMO2 can regulate different cellular signaling pathways by mediating protein-protein interactions in different tumors [ 7 ]. Research has demonstrated that Lmo2 is capable of promoting the growth of self-renewing preleukemic stem cells (pre-LSCs) and the onset of ETP-ALL [ 32 ].…”

“…LMO2 interacts directly with LDB1 in AML cell lines [26] and LDB1 is required for cell survival LMO2 may contribute to cancer development by mediating protein-protein interactions [7]. To identify the proteins interacting with LMO2 in AML, we overexpressed HA-labeled LMO2 in 293 T cells and carried out co-immunoprecipitation.…”

“…The LIM domain of the LMO2 protein can mediate protein-protein interaction, while curl, zinc finger and SH3 are the favorable interaction domains of LMO2. In addition, members containing these domains have significantly abundant functions in cancer, speculating that the main functions of LMO2 are involved in carcinogenesis [ 7 ]. Previous studies have shown that LMO2 mutations in the non-coding sites of T-ALL cell lines could result in the formation of abnormal promoters and enhancers, which drive the overexpression of LMO2 in patients with T-ALL [ 8 ].…”