The Controversial Roles of ADP-Ribosyl Hydrolases MACROD1, MACROD2 and TARG1 in Carcinogenesis

Cancers
Karla L H FeijsRoko Žaja

Abstract

Post-translational modifications (PTM) of proteins are crucial for fine-tuning a cell's response to both intracellular and extracellular cues. ADP-ribosylation is a PTM, which occurs in two flavours: modification of a target with multiple ADP-ribose moieties (poly(ADP-ribosyl)ation or PARylation) or with only one unit (MARylation), which are added by the different enzymes of the PARP family (also known as the ARTD family). PARylation has been relatively well-studied, particularly in the DNA damage response. This has resulted in the development of PARP inhibitors such as olaparib, which are increasingly employed in cancer chemotherapeutic approaches. Despite the fact that the majority of PARP enzymes catalyse MARylation, MARylation is not as well understood as PARylation. MARylation is a dynamic process: the enzymes reversing intracellular MARylation of acidic amino acids (MACROD1, MACROD2, and TARG1) were discovered in 2013. Since then, however, little information has been published about their physiological function. MACROD1, MACROD2, and TARG1 have a 'macrodomain' harbouring the catalytic site, but no other domains have been identified. Despite the lack of information regarding their cellular roles, there are a number of stud...Continue Reading

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Citations

Dec 2, 2020·Cancers·Nicola Curtin, Péter Bai
Jan 16, 2021·Journal of Zhejiang University. Science. B·Lily YuXiaochun Yu
Feb 14, 2021·Cells·Kerryanne CrawfordIvan Ahel
Feb 25, 2021·Molecular Genetics & Genomic Medicine·Hye-Rim KimYong-Bin Eom
Mar 12, 2021·Nucleic Acids Research·Lisa WeixlerRoko Žaja
Mar 21, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Fabio AimiMichael O Hottiger
Apr 4, 2021·Cells·Ann-Katrin Hopp, Michael O Hottiger

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Methods Mentioned

BETA
AlphaScreen
xenograft
dissect

Software Mentioned

cBioPortal

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