Poly(ADP-ribose)-dependent ubiquitination and its clinical implications

Christina A Vivelo; Vinay Ayyappan; Anthony K L Leung

doi:10.1016/j.bcp.2019.05.006

Poly(ADP-ribose)-dependent ubiquitination and its clinical implications

Biochem Pharmacol. 2019 Sep:167:3-12. doi: 10.1016/j.bcp.2019.05.006. Epub 2019 May 8.

Authors

Christina A Vivelo¹, Vinay Ayyappan², Anthony K L Leung³

Affiliations

¹ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: anthony.leung@jhu.edu.

Abstract

ADP-ribosylation-the addition of one or multiple ADP-ribose units onto proteins-is a therapeutically important post-translational modification implicated in cancer, neurodegeneration, and infectious diseases. The protein modification regulates a broad range of biological processes, including DNA repair, transcription, RNA metabolism, and the structural integrity of nonmembranous structures. The polymeric form of ADP-ribose, poly(ADP-ribose), was recently identified as a signal for triggering protein degradation through the ubiquitin-proteasome system. Using informatics analyses, we found that these ubiquitinated substrates tend to be low abundance proteins, which may serve as rate-limiting factors within signaling networks or metabolic processes. In this review, we summarize the current literature on poly(ADP-ribose)-dependent ubiquitination (PARdU) regarding its biological mechanisms, substrates, and relevance to diseases.

Keywords: ADP-ribosylation; Poly(ADP-ribose); Poly(ADP-ribose)-dependent ubiquitination; Protein degradation; Rate-limiting factors; Tankyrase; Ubiquitin-proteasome system.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
DNA Repair / physiology*
Humans
Poly Adenosine Diphosphate Ribose / chemistry*
Poly Adenosine Diphosphate Ribose / metabolism*
Protein Structure, Secondary
Ubiquitination / physiology*

Substances

Poly Adenosine Diphosphate Ribose

Abstract

Publication types

MeSH terms

Substances

Grants and funding