Microtubule-associated protein 1 light chain 3 interacts with and contributes to growth inhibiting effect of PML

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Abstract

Previously we reported that the expression of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha) fusion gene, which is caused by specific translocation (15;17) in acute promyelocytic leukemia, can enhance constitutive autophagic activity in leukemic and nonleukemic cells, and PML overexpression can sequestrate part of microtubule-associated protein light chain 3 (LC3) protein in PML nuclear bodies, suggesting that LC3 protein also distributes into nuclei although it is currently thought to function primarily in the cytoplasm, the site of autophagosomal formation. However, its potential significance of nucleoplasmic localizations remains greatly elusive. Here we demonstrate that PML interacts with LC3 in a cell type-independent manner as assessed by Co-IP assay and co-localization observation. Overexpressed PML significantly coprecipitates with endogenous and nuclear LC3 protein. Furthermore, a fraction of endogenous PML protein is found to be co-localized with LC3 protein under steady state condition, which is further enhanced by IFNalpha induction, indicating that PML up-regulation potentiates this interaction. Additionally, DsRed-PML associates with EGFP-LC3 during telophase and G1 phase but not in metaphase and anaphase. Two potential LC3-interacting region (LIR) motifs in PML are required for interaction of PML with LC3 while this association is independent of autophagic activity. Finally, we show that interaction between PML and LC3 contributes to cell growth inhibition function of PML. Considering that PML is an important tumor suppressor, we propose that nuclear portion of LC3 protein may associate with PML to control cell growth for prevention and inhibition of cancer occurrence and development.

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He, W., Hu, C. X., Hou, J. K., Fan, L., Xu, Y. W., Liu, M. H., … Huang, Y. (2014). Microtubule-associated protein 1 light chain 3 interacts with and contributes to growth inhibiting effect of PML. PLoS ONE, 9(11). https://doi.org/10.1371/journal.pone.0113089

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