TY - JOUR
T1 - Poly(ADP-ribose)-dependent ubiquitination and its clinical implications
AU - Vivelo, Christina A.
AU - Ayyappan, Vinay
AU - Leung, Anthony K.L.
N1 - Funding Information:
We thank Mr. Lyle McPherson for making the inserts of Fig. 3 and the members of the Leung laboratory for critical inputs to this manuscript. This work was partly supported by R01GM104135 (A.K.L.L.), U54GM103520 (A.K.L.L.) and T32CA009110 (C.A.V) from National Institutes of Health, and the American Cancer Society Research Scholar Award RSG-16-062-01-RMC (A.K.L.L.).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - ADP-ribosylation
KW - Poly(ADP-ribose)
KW - Poly(ADP-ribose)-dependent ubiquitination
KW - Protein degradation
KW - Rate-limiting factors
KW - Tankyrase
KW - Ubiquitin-proteasome system
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U2 - 10.1016/j.bcp.2019.05.006
DO - 10.1016/j.bcp.2019.05.006
M3 - Review article
C2 - 31077644
AN - SCOPUS:85065528576
SN - 0006-2952
VL - 167
SP - 3
EP - 12
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -