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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

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Published on: July 17, 2020

Nuclear PKM2 regulates the Warburg effect.

Weiwei Yang1, Zhimin Lu

  • 1Brain Tumor Center; Department of Neuro-Oncology; The University of Texas MD Anderson Cancer Center; Houston, TX USA.

Cell Cycle (Georgetown, Tex.)
|September 10, 2013
PubMed
Summary
This summary is machine-generated.

Pyruvate kinase M2 (PKM2) acts as a nuclear histone kinase, promoting cancer by upregulating c-Myc and cyclin D1. Targeting nuclear PKM2 offers a potential strategy for cancer treatment.

Keywords:
ERKPKM1PKM2c-Myccyclin D1histonethe Warburg effect

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Pyruvate kinase is a key enzyme in glycolysis.
  • PKM2, unlike PKM1, is implicated in the Warburg effect and tumorigenesis.
  • The precise mechanisms by which PKM2 drives these processes are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms by which PKM2 regulates the Warburg effect and tumorigenesis.
  • To investigate the role of ERK1/2 phosphorylation and subsequent PKM2 modifications in cancer progression.

Main Methods:

  • Investigated the phosphorylation of PKM2 by ERK1/2.
  • Examined the role of PIN1 in PKM2 isomerization.
  • Assessed the nuclear translocation and histone kinase activity of PKM2.
  • Analyzed the effects of nuclear PKM2 on c-Myc and cyclin D1 expression.

Main Results:

  • ERK1/2 phosphorylates PKM2, but not PKM1.
  • Phosphorylation induces PIN1-dependent cis-trans isomerization, converting PKM2 to a monomer.
  • Monomeric PKM2 translocates to the nucleus and functions as a histone kinase.
  • Nuclear PKM2 upregulates c-Myc and cyclin D1, promoting the Warburg effect and cell cycle progression.

Conclusions:

  • Nuclear PKM2 plays a critical role in promoting tumorigenesis.
  • PKM2's function as a nuclear histone kinase is essential for cancer cell proliferation.
  • Targeting nuclear PKM2 presents a promising therapeutic strategy for human cancers.