Implication and Regulation of AMPK during Physiological and Pathological Myeloid Differentiation.

摘要: AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine consisting of the arrangement various α β, and γ isoforms that are expressed differently depending on tissue or cell lineage. AMPK one major sensors energy status in mammalian cells as such plays essential roles regulation cellular homeostasis, metabolism, growth, differentiation, apoptosis, autophagy. activated by two upstream kinases, tumor suppressor liver B1 (LKB1) calcium/calmodulin-dependent 2 (CAMKK2) through phosphorylation Thr172, leading to its activation. In addition, inhibits mTOR pathway activation tuberous sclerosis (TSC2) causes direct unc-51-like autophagy activating 1 (ULK1) via Ser555, thus promoting initiation Although it well established can control differentiation different lineages, including hematopoietic stem (HSCs), progenitors, mature cells, role regarding myeloid less documented. The monocytes into macrophages triggered colony stimulating factor (CSF-1), process during which both caspase (independently apoptosis induction) AMPK-dependent stimulation necessary, noticeable example involvement physiological cells. present review focuses pathological mechanisms induction will also be addressed, has been shown important for malignancies (myeloid leukemia dysplasia) characterized profound defects establishment proper programs. Reinduction normal emerged valuable promising therapeutic strategy. As seems exert key notably autophagy, we discuss potential target this pro-differentiating anti-leukemic strategy malignancies.