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Proteomic Analysis of the Downstream Signaling Network of PARP1

Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP-ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is activated upon sensing nicked DNA. Once activated, PARP1 is responsible for the synthesis of a large number of PARylated proteins and initiation of the DNA damage response mechanisms. This observation provided the rationale for developing PARP1 inhibitors for the treatment of human malignancies. Indeed, three PARP1 inhibitors (Olaparib, Rucaparib, and Niraparib) have recently been approved by the Food and Drug Administration for the treatment of ovarian cancer. Moreover, in 2017, both Olaparib and Niraparib have also been approved for the treatment of fallopian tube cancer and primary peritoneal cancer. Despite this very exciting progress in the clinic, the basic signaling mechanism that conne...

Autoren:   Yuanli Zhen; Yonghao Yu
Journal:   Biochemistry
Jahrgang:   2018
DOI:   10.1021/acs.biochem.7b01022
Erscheinungsdatum:   19.01.2018
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