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Updated: Mar 24, 2026

Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation
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Human Peripheral Blood Neutrophil Isolation for Interrogating the Parkinson's Associated LRRK2 Kinase Pathway by Assessing Rab10 Phosphorylation

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Parkin Regulates the Activity of Pyruvate Kinase M2

Kun Liu1, Fanzhou Li1, Haichao Han1

  • 1From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center and Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing 100191, China.

The Journal of Biological Chemistry
|March 16, 2016
PubMed

Insights

Parkin, a Parkinson disease protein, regulates cancer cell metabolism by modifying pyruvate kinase M2 (PKM2). This discovery offers new therapeutic insights for both Parkinson disease and cancer.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Parkin, a ubiquitin E3 ligase, is linked to Parkinson disease and cancer.
  • Mutations in Parkin inhibit tumor cell growth, suggesting a role in malignancy.

Purpose of the Study:

  • To identify substrates of Parkin involved in tumor cell metabolism.
  • To elucidate the regulatory mechanism of Parkin on glycolysis and cell metabolism.

Main Methods:

  • Biochemical purification to identify Parkin substrates.
  • In vitro and in vivo interaction studies between Parkin and pyruvate kinase M2 (PKM2).
  • Assessment of PKM2 ubiquitylation and enzymatic activity changes.

Main Results:

  • Pyruvate kinase M2 (PKM2) was identified as a unique substrate for Parkin.
  • Parkin interacts with PKM2, with increased interaction under glucose starvation.
  • Parkin-mediated ubiquitylation of PKM2 reduces its enzymatic activity, impacting glycolysis.

Conclusions:

  • Parkin plays a novel role in regulating tumor cell metabolism through PKM2.
  • Understanding Parkin's function in cell metabolism provides new therapeutic avenues for Parkinson disease and cancer.
Keywords:
Parkinson diseaseglycolysisparkinpyruvate kinasepyruvate kinase M2ubiquitylation (ubiquitination)

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