Journal Article10.1038/NMETH.2603
Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome
340
TL;DR: A method to characterize the human aspartic acid– and glutamic acid–ADP-ribosylated proteome was described and it was confirmed that iniparib had a negligible effect on PARP activity in intact cells.
read more
Abstract: Poly(ADP-ribosyl)ation is catalyzed by a family of enzymes known as PARPs. We describe a method to characterize the human aspartic acid- and glutamic acid-ADP-ribosylated proteome. We identified 1,048 ADP-ribosylation sites on 340 proteins involved in a wide array of nuclear functions; among these were many previously unknown PARP downstream targets whose ADP-ribosylation was sensitive to PARP inhibitor treatment. We also confirmed that iniparib had a negligible effect on PARP activity in intact cells.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
TL;DR: New findings on the diverse roles of PARPs in chromatin regulation, transcription, RNA biology, and DNA repair have been complemented by recent advances that link ADP-ribosylation to stress responses, metabolism, viral infections, and cancer.
Status of Large-scale Analysis of Post-translational Modifications by Mass Spectrometry
Jesper V. Olsen,Matthias Mann +1 more
TL;DR: In this overview for the special PTM issue of Molecular and Cellular Proteomics, it is taken stock of where MS-based proteomics stands in the large-scale analysis of protein modifications.
589
A mass-tolerant database search identifies a large proportion of unassigned spectra in shotgun proteomics as modified peptides
Joel M. Chick,Deepak Kolippakkam,David P. Nusinow,Bo Zhai,Ramin Rad,Edward L. Huttlin,Steven P. Gygi +6 more
TL;DR: It is concluded that at least one-third of unassigned spectra arise from peptides with substoichiometric modifications, and an ultra-tolerant Sequest database search that allows peptide matching even with modifications of unknown masses is used.
Family-wide analysis of poly(ADP-ribose) polymerase activity
TL;DR: In this article, the majority of PARPs generate MAR, not PAR, and demonstrate that the H-Y-E motif is not the sole indicator of PARP activity, suggesting that the sequence and structural constraints limiting PARPs to MAR synthesis do not limit their ability to modify canonical amino-acid targets.
Poly(ADP-ribosyl)ation by PARP1: reaction mechanism and regulatory proteins.
TL;DR: Old and up-to-date literature is summarized to clarify several points concerning PARylation mechanism and discuss different ways for regulation of PAR synthesis by accessory proteins reported thus far.
References
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Hannah Farmer,Nuala McCabe,Christopher J. Lord,Andrew Tutt,Andrew Tutt,Damian A. Johnson,Tobias B. Richardson,Manuela Santarosa,Krystyna J. Dillon,Ian Hickson,Charlotte Knights,Niall M. B. Martin,Stephen P. Jackson,Graeme C. M. Smith,Alan Ashworth +14 more
TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
6.6K
A tissue-specific atlas of mouse protein phosphorylation and expression.
Edward L. Huttlin,Mark P. Jedrychowski,Joshua E. Elias,Tapasree Goswami,Ramin Rad,Sean A. Beausoleil,Judit Villén,Wilhelm Haas,Mathew E. Sowa,Steven P. Gygi +9 more
TL;DR: The data suggest that the "typical" phosphoprotein is widely expressed yet displays variable, often tissue-specific phosphorylation that tunes protein activity to the specific needs of each tissue, and is offered as an online resource for the biological research community.
1.7K
Systematic and Quantitative Assessment of the Ubiquitin-Modified Proteome
Woong Kim,Eric J. Bennett,Edward L. Huttlin,Ailan Guo,Jing Li,Anthony Possemato,Mathew E. Sowa,Ramin Rad,John Rush,Michael J. Comb,J. Wade Harper,Steven P. Gygi +11 more
TL;DR: The human ubiquitin-modified proteome is characterized using a monoclonal antibody that recognizes diglycine (diGly)-containing isopeptides following trypsin digestion and it is demonstrated that quantitative diGly proteomics can be utilized to identify substrates for cullin-RING ubiquitIn ligases.
1.6K
PARP inhibition: PARP1 and beyond
TL;DR: What is known about the structures and functions of the family ofPARP enzymes are reviewed, and a series of questions that should be addressed are outlined to guide the rational development of PARP inhibitors as anticancer agents.
1.3K
Phosphoproteomic Analysis Identifies Grb10 as an mTORC1 Substrate That Negatively Regulates Insulin Signaling
Yonghao Yu,Sang-Oh Yoon,George Poulogiannis,Qian Yang,Xiaoju Max Ma,Judit Villén,Neil Kubica,Gregory R. Hoffman,Lewis C. Cantley,Steven P. Gygi,John Blenis +10 more
TL;DR: A search for substrates of a growth-promoting kinase revealed a regulatory feedback loop involved in tumor suppression, and large-scale quantitative phosphoproteomics experiments were used to define the signaling networks downstream of mTORC1 and m TORC2.