Mitotic kinase dynamics of the active form of AMPK (Phospho-AMPKαThr172) in human cancer cells

Vázquez-Martín, Alejandro; López-Bonet, Eugeni; Oliveras‐Ferraros, Cristina; Pérez-Martínez, Maria Carmen; Bernadó, Luis; Menéndez, Javier A.

doi:10.4161/cc.8.5.7787

Cited by 48 publications

(56 citation statements)

References 17 publications

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“…7 Intriguingly, we recently reported that the Threonine 172-phosphorylated active form of the α-catalytic subunit of AMPK (PP-AMPKα Thr172 ) is specifically upregulated within mitotic areas in human cancer tissues. 8 Careful immunohistochemical analyses confirmed that PP-AMPKα Thr172 exhibits a series of choreographed movements at precise nucleocytoplasmic locations and at specific times from prophase to telophase. Biochemical analyses revealed further that kinetic changes of AMPKα activation occur in a cell cycle phase-dependent manner and strictly in parallel to that of well-characterized M-phase activated kinases.…”

Section: Ampkmentioning

confidence: 99%

AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor

et al. 2009

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Section: Ampkmentioning

confidence: 99%

AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor

et al. 2009

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“…13 In this regard, we have previously reported that the active form of AMPK directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis. [32][33][34] Recently, we have established that polo-like kinase 1 (PLK1) is a novel regulator of AMPK activation at the mitotic apparatus. 35 These findings, altogether, may suggest the existence of a functional link connecting PLK1, AMPK and P-Raptor Ser722 during mitosis.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs)

Vázquez-Martín¹,

Cufí²,

Oliveras‐Ferraros³

et al. 2011

Cell Cycle

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“…30 When analyzing mitotic areas of human cancer tissues, we have recently shown that, upon activating phosphorylation of Thr172 at its α catalytic subunit, AMPK distinctively organized in the form of a distinct punctuate staining during mitosis and cytokinesis. 31 Importantly, eye-catching P-AMPK Thr172 spots were not distributed randomly in the cytoplasm of mitotic cells but rather appeared to display choreographed series of movements at precise nucleo-cytoplasmic locations and specific times from prophase to telophase in vivo. Moreover, the kinetic of changes in in vitro AMPK activation was found to occur in a cell cycle phase-dependent manner and strictly in parallel to that of well-characterized mitotic kinases such as Aurora B.…”

Section: Introductionmentioning

confidence: 99%

The active form of the metabolic sensor AMP-activated protein kinase α (AMPKα) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis

Vázquez-Martín

Oliveras‐Ferraros²,

Menéndez³

2009

Cell Cycle

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(2009) The active form of the metabolic sensor AMP-activated protein kinase α (AMPKα) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis, Cell Cycle, 8:15, 2385Cycle, 8:15, -2398 The metabolic rheostat AMP-activated protein kinase (AMPK) is unexpectedly required for proper cell division and faithful chromosomal segregation during mitosis. Although it is conceptually attractive to assume that AMPK-interpreted microenvironmental bioenergetics may strictly engage cell's energy status, cell grow, and cell division to avoid that energy stresses trigger cell death, the ultimate framework of AMPK activity towards chromosomal and cytoskeletal mitotic regulation is a question that remains unanswered. We herein reveal that the active form of the α-catalytic AMPK subunit (P-AMPKα Thr172 )-but not its total form (AMPKα)-transiently associates with several mitotic structures including centrosomes, spindle poles, the central spindle midzone and the midbody throughout all of the mitotic stages and cytokinesis in human cancer-derived epithelial cells. At prophase, P-AMPKα Thr172 associates with the two asters of microtubules that begin to nucleate from mature centrosomes. The overlapping localization of P-AMPKα Thr172 with the mitotic centrosomal Aurora-A kinase is also apparent on the microtubules near the spindle poles in metaphase and in early anaphase. This Aurora A-like centrosomal localization of P-AMPKα Thr172 cannot be detected following chromatid separation following anaphase-telophase transition. Rather, toward the end of anaphase and in telophase P-AMPKα Thr172 reactivity exhibited a similar but not identical localization to that occupied by the bona fide chromosomal passenger proteins INCENCP and Aurora-B. This localization of P-AMPKα Thr172 at the central spindle and midbody persisted during the furrowing process and, at the completion of telophase, staining of P-AMPKα Thr172 as doublet was apparent on either side of the midbody within the intercellular cytokinetic bridge. An identical mitotic geography of P-AMPKα Thr172 was observed in cancer cells lacking the AMPK kinase LKB1, in non-cancerous human epithelial cells, and in mouse fibroblasts. The active form of AMPKα bound to the mitotic apparatus may physically tether the bioenergetic state of a cell to the four-dimensional regulation of the chromosomal and cytoskeletal mitotic events, thus suggesting a putative cytokinetic suppressor function. In this newly discovered scenario, we suggest a primordial mitotic role for the α catalytic AMPK subunit in the eukaryotic evolutionary process as it may ensure, at the cell level, an exquisite coordination between sensing of energy resources and the fundamental biological process of genome division.

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Mitotic kinase dynamics of the active form of AMPK (Phospho-AMPKαThr172) in human cancer cells

Cited by 48 publications

References 17 publications

AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor

AMPK: Evidence for an energy-sensing cytokinetic tumor suppressor

Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs)

The active form of the metabolic sensor AMP-activated protein kinase α (AMPKα) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis

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