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ADP-ribosylarginine hydrolase regulates cell proliferation and tumorigenesis

Jiro Kato1, Jianfeng Zhu, Chengyu Liu

  • 1Office of Biostatistics Research, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.

Cancer Research
|June 24, 2011
PubMed

Insights

Deleting the ADP-ribosylarginine hydrolase (ARH1) enzyme, which controls protein ADP-ribosylation, increases cancer susceptibility. Loss of ARH1 function in mice leads to spontaneous tumor formation, highlighting its role in cancer suppression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Protein ADP-ribosylation is a reversible posttranslational modification with unclear roles in cancer.
  • The enzyme ADP-ribosylarginine hydrolase (ARH1) removes mono-ADP-ribose from proteins, cleaving the ADP ribose-protein bond.

Purpose of the Study:

  • To investigate the role of ARH1 in cancer susceptibility by studying mice genetically deficient in this enzyme.
  • To determine the consequences of ARH1 deletion on tumor development and progression.

Main Methods:

  • Generated and analyzed ARH1 knockout (ARH1(-/-)) and heterozygous (ARH1(+/-)) mice.
  • Assessed cancer susceptibility, tumor formation (lymphomas, adenocarcinomas), and metastasis in ARH1-deficient mice compared to wild-type (ARH1(+/+)).
  • Examined proliferation rates of ARH1(-/-) cells and ARH1(+/-) tumors for evidence of gene function loss.

Main Results:

  • ARH1(-/-) cells exhibited higher proliferation rates compared to wild-type cells.
  • ARH1(-/-) and ARH1(+/-) mice developed spontaneous lymphomas, adenocarcinomas, and metastases at higher frequencies than wild-type mice.
  • Tumors in ARH1(+/-) mice showed mutation or loss of heterozygosity of the remaining wild-type ARH1 allele, confirming the link between ARH1 absence and tumor formation.

Conclusions:

  • ARH1 plays a critical role in suppressing cancer development.
  • Proper regulation of protein ADP-ribosylation by ARH1 is essential for preventing tumor formation and progression.
  • Loss of ARH1 function is directly correlated with increased cancer susceptibility.

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