Pyruvate kinase isoenzymes in chromatin extracts of Ehrlich ascites tumour, Morris hepatoma 7777 and normal mouse and rat livers

Gumińska, M; Stachurska, M.; Ignacak, Jan

doi:10.1016/0304-4165(88)90113-4

Cited by 25 publications

(12 citation statements)

References 21 publications

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“…Because PKM2 is predominantly expressed in tumor cells (18)(19)(20), we wanted to know whether nuclear translocation is sufficient to induce apoptosis and if this effect is isoform specific. To address this question, we fused PKM2 and PKM1 isoforms to GFP or SV40 large T-antigen nuclear localization signal (NLS)-tagged YFP and used YFP protein alone as a control.…”

Section: Resultsmentioning

confidence: 99%

“…The M2 type (PKM2) is considered to be expressed predominantly in the fetus, in neoplastic tissues, and in undifferentiated or proliferating cells but is also found in some adult tissues as a tetrameric form (16,17). During tumorigenesis, the tissue characteristic PK isoform is replaced by PKM2 that is present predominantly as a dimer (18) and seems to represent a tumor-specific form (19,20). The dissociation of the tetrameric to the dimeric form can be induced by oncoproteins (21).…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Translocation of the Tumor Marker Pyruvate Kinase M2 Induces Programmed Cell Death

et al. 2007

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Cancer cells often fail to respond to stimuli that normally activate their intrinsic apoptotic machinery. Moreover, they are able to adapt to hypoxia by changing their glycolytic rate. Pyruvate kinase (PK) is a rate-limiting enzyme in glycolysis that is converted to a less active dimer form of PKM2 isoenzyme during oncogenesis. Here, we show that both somatostatin and the structural analogue TT-232 interact with the PKM subtype. We further show that the PKM2 is translocated to the nucleus in response to TT-232 and different apoptotic agents. Nuclear translocation of PKM2 is sufficient to induce cell death that is caspase independent, isoform specific, and independent of its enzymatic activity. These results show that the tumor marker PKM2 plays a general role in caspaseindependent cell death of tumor cells and thereby defines this glycolytic enzyme as a novel target for cancer therapy development. [Cancer Res 2007;67(4):1602-8]

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nuclear Translocation of the Tumor Marker Pyruvate Kinase M2 Induces Programmed Cell Death

et al. 2007

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“…A monomeric form of M2-PK with low enzymatic activity was previously described as a cytosolic thyroid hormonebinding protein [Kato et al, 1989], and a subsequent study suggested that monomeric M2-PK has a role in the regulation of thyroid hormone receptor-dependent transcription [Ashizawa and Cheng, 1992]. Previous work also provided evidence for DNA-binding and histone H1 kinase activity of M2-PK [Guminska et al, 1988], and recent work demonstrated that M2-PK can exist as a nuclear protein. Thus, interleukin-3 induces nuclear translocation of M2-PK and this enhances cell proliferation [Hoshino et al, 2007].…”

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confidence: 92%

The SUMO‐E3 ligase PIAS3 targets pyruvate kinase M2

Spoden

Morandell

Ehehalt

et al. 2009

J of Cellular Biochemistry

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Pyruvate kinase M2 (M2-PK) controls the rate-limiting step at the end of the glycolytic pathway in normal proliferating and tumor cells. Other functions of M2-PK in addition to its role in glycolysis are little understood. The aim of this study was to identify new cellular interaction partners of M2-PK in order to discover novel links between M2-PK and cellular functions. Here we show that the SUMO-E3 ligase protein PIAS3 (inhibitor of activated STAT3) physically interacts with M2-PK and its isoenzyme M1-PK. Moreover, we demonstrate that endogenous SUMO-1-M2-PK conjugates exist in mammalian cells. Furthermore, we show that transient expression of PIAS3 but not the RING domain mutant PIAS3 (C299S, H301A) is consistent with nuclear localization of M2-PK and PIAS3 and M2-PK partially co-localize in the nucleus of these cells. This study suggests a link between PIAS3 and nuclear pyruvate kinase.

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“…The liver-specific enzymes fructokinase and aldolase B are lost or have only low activities depending on the stage of dedifferentiation (1,6). The kinetic properties of hexokinase are changed and some feedback control mechanisms that regulate glycolysis in normal tissue do not work in hepatoma cells (7,8).Recently it was shown that fructose as a carbon source is capable of maintaining the viability of hepatocytes under hypoxic conditions (9, 10). In hepatomas, as in most other solid tumors, extensive areas of hypoxia may exist and the cells in these areas can maintain their energy production solely by anaerobic glycolysis (1 1,12).…”

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confidence: 99%

mentioning

confidence: 99%

Differences in glycolytic capacity and hypoxia tolerance between hepatoma cells and hepatocytes

et al. 1991

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Viability, glycolytic capacity and energy metabolism under anaerobic conditions were studied in the hepatoma cell lines HTC, FU5 and HepG2 and in rat and human hepatocytes using glucose and fructose as glycolytic precursors. During 6 hr of anaerobic incubation without additional substrate, viability decreased rapidly in FU5 and HTC cells, whereas viability of HepG2 cells was not significantly affected. In all tumor cells, 10 mmol/L glucose prevented hypoxic cell injury almost completely. Lactate formation from glucose was about five times higher than in hepatocytes under these circumstances. ATP content of the tumor cells remained almost constant under anaerobic conditions in the presence of glucose. Ten millimoles per liter of fructose diminished glycolysis in the hepatoma cells compared with glucose, ranging from 87% reduction in HTC cells to 43% reduction in HepG2 cells. Accordingly, ATP content decreased rapidly in the FU5 and slowly in the HepG2 cells. Viability was strongly diminished in the HTC and FU5 cells in the presence of fructose, whereas in the HepG2 cells no effect of fructose on viability was detectable. In contrast to the hepatoma cells, rat and human hepatocytes exhibited higher rates of anaerobic glycolysis in the presence of fructose and thus were able to maintain their viability under these conditions. These differences in glycolytic capacity, energy metabolism and hypoxia tolerance of hepatoma cells compared with hepatocytes may be used for the treatment of liver cancer by isolated liver perfusion and ex situ revision of the organ.

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Pyruvate kinase isoenzymes in chromatin extracts of Ehrlich ascites tumour, Morris hepatoma 7777 and normal mouse and rat livers

Cited by 25 publications

References 21 publications

Nuclear Translocation of the Tumor Marker Pyruvate Kinase M2 Induces Programmed Cell Death

Nuclear Translocation of the Tumor Marker Pyruvate Kinase M2 Induces Programmed Cell Death

The SUMO‐E3 ligase PIAS3 targets pyruvate kinase M2

Differences in glycolytic capacity and hypoxia tolerance between hepatoma cells and hepatocytes

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