AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor

Ser2481-autophosphorylated mTOR colocalizes with chromosomal passenger proteins during mammalian cell cytokinesis

“…Using an automated confocal imaging system for high-resolution images and 3-D reconstructions, we first explored the spatiotemporal dynamics of phospho-mTOR Ser2481 during the G 2 /M stage of the cell cycle in HeLa cancer cells. Similar to that observed when analyzing the spatiotemporal dynamics of phospho-AMPK Thr172 during mitosis and cytokinesis, [18][19][20][21][22][23] we observed a previously unrecognized pattern of transient associations between phosphomTOR Ser2481 and specific mitotic structures during mitotic chromosome condensation/segregation and cytokinesis, including the central spindle midzone and the midbody (Fig. 2).…”

“…All spindle midzone and the midbody, throughout all of the mitotic stages and during the furrowing process in cytokinesis. [18][19][20][21][22][23] Indeed, a trimeric complex of AMPK containing the γ 2 regulatory subunit appears to become selectively activated in the cytokinetic apparatus and to be directly linked to mitotic processes. 22,24,25 Other groups have confirmed these observations, [26][27][28] and we now know that mitotic AMPK regulates mitotic spindle orientation through phosphorylation of the myosin regulatory light chain, and that it ensures the normal recruitment of myosin molecules into the contractile ring structure to allow the proper transition from metaphase to anaphase and the completion of cytokinesis.…”

AMP-activated protein kinase (AMPK) beyond metabolism

“…89,91 We have made similar observations in lung cancer cells (A549) where phosphorylated AMPK α1 and α2 Thr172 was associated with centrosomes in prophase, spindle poles in metaphase and cleavage furrow in anaphase and telophase (Fig. 6A).…”

Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells

“…89 Sixth, p53 negatively regulates the expression of glucose transporters (e.g., SLC2A12/GLUT12, SLC2A1/GLUT1) and the master transcription factor c-Myc, which is another crucial regulator of p53, to initiate tumor formation in epithelial cells by blocking the differentiation of p53-deficient stem cells. 74,77 Herein, we describe for the first time the function of the metabolic tumor suppressor AMPK 47,78 in terms of somatic reprogramming efficiency to a pluripotent state. AMPK appears to operate upstream of the most common pathways associated with human cancers, suppression of p53 and activation of c-Myc, because AMPK-activating drugs fully impede the reprogramming of somatic cells to iPSCs regardless of the p53 status and/or the inclusion of c-Myc in the reprogramming cocktail.…”