TY  - JOUR
AU  - Mandić, Miloš
AU  - Misirkić Marjanović, Maja
AU  - Vučićević, Ljubica
AU  - Jovanović, Maja
AU  - Bošnjak, Mihajlo
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Ćirić, Darko
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320522001813
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35304128
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4947
AB  - We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.
PB  - Elsevier Inc.
T2  - Life Sciences
T1  - MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.
VL  - 297
DO  - 10.1016/j.lfs.2022.120481
SP  - 120481
ER  - 

@article{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Jovanović, Maja and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2022",
abstract = "We investigated the mechanisms and the role of autophagy in the differentiation of HL-60 human acute myeloid leukemia cells induced by protein kinase C (PKC) activator phorbol myristate acetate (PMA). PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by cell-cycle arrest accompanied by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by the increase in intracellular acidification, accumulation/punctuation of autophagosome marker LC3-II, and the increase in autophagic flux. PMA also increased nuclear translocation of autophagy transcription factors TFEB, FOXO1, and FOXO3, as well as the expression of several autophagy-related (ATG) genes in HL-60 cells. PMA failed to activate autophagy inducer AMP-activated protein kinase (AMPK) and inhibit autophagy suppressor mechanistic target of rapamycin complex 1 (mTORC1). On the other hand, it readily stimulated the phosphorylation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) via a protein kinase C-dependent mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear translocation of TFEB and FOXO1/3, ATG expression, dissociation of pro-autophagic beclin-1 from its inhibitor BCL2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells. Pharmacological or genetic inhibition of autophagy also blocked PMA-induced macrophage differentiation of HL-60 cells. Therefore, MAP kinases ERK and JNK control PMA-induced macrophage differentiation of HL-60 leukemia cells through AMPK/mTORC1-independent, TFEB/FOXO-mediated transcriptional and beclin-1-dependent post-translational activation of autophagy.",
publisher = "Elsevier Inc.",
journal = "Life Sciences",
title = "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.",
volume = "297",
doi = "10.1016/j.lfs.2022.120481",
pages = "120481"
}

Mandić, M., Misirkić Marjanović, M., Vučićević, L., Jovanović, M., Bošnjak, M., Perović, V., Ristić, B., Ćirić, D., Harhaji-Trajković, L.,& Trajković, V.. (2022). MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences
Elsevier Inc.., 297, 120481.
https://doi.org/10.1016/j.lfs.2022.120481

Mandić M, Misirkić Marjanović M, Vučićević L, Jovanović M, Bošnjak M, Perović V, Ristić B, Ćirić D, Harhaji-Trajković L, Trajković V. MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells.. in Life Sciences. 2022;297:120481.
doi:10.1016/j.lfs.2022.120481 .

Mandić, Miloš, Misirkić Marjanović, Maja, Vučićević, Ljubica, Jovanović, Maja, Bošnjak, Mihajlo, Perović, Vladimir, Ristić, Biljana, Ćirić, Darko, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "MAP kinase-dependent autophagy controls phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells." in Life Sciences, 297 (2022):120481,
https://doi.org/10.1016/j.lfs.2022.120481 . .