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Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein

Nobukazu Shimada1, Toshie Shinagawa, Shunsuke Ishii

  • 1Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|February 27, 2008
PubMed

Insights

Cytoplasmic promyelocytic leukemia (PML) protein interacts with pyruvate kinase M2 (PKM2), a key enzyme in cancer metabolism. This interaction suppresses PKM2 activity, impacting glucose utilization and lactate production in breast cancer cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Promyelocytic leukemia (PML) protein functions as a tumor suppressor, primarily in the nucleus.
  • PML protein also localizes to the cytoplasm, but its role there is not well understood.
  • Cancer cells exhibit high glycolytic rates, yet the underlying mechanisms are unclear.

Purpose of the Study:

  • To investigate the function of cytoplasmic PML (cPML) in cancer metabolism.
  • To explore the interaction between cPML and M2-type pyruvate kinase (PKM2).

Main Methods:

  • Utilized MCF-7 breast cancer cells.
  • Generated a cytoplasmic PML mutant (PML-2KA) by altering nuclear localization signals.
  • Assessed PKM2 activity, lactate accumulation, and protein interactions.

Main Results:

  • Cytoplasmic PML (cPML) directly interacts with PKM2.
  • Over-expression of PML-2KA in MCF-7 cells suppressed PKM2 activity and lactate accumulation.
  • PML-2KA specifically inhibited the active tetrameric form of PKM2.

Conclusions:

  • Cytoplasmic PML plays a role in regulating tumor metabolism.
  • The interaction between cPML and PKM2 influences glucose metabolism pathways in cancer.

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