Last update 01 Nov 2024

PARP10

Last update 01 Nov 2024

Basic Info

Synonyms

ADP-ribosyltransferase diphtheria toxin-like 10, ARTD10, FLJ14464

+ [5]

Introduction

ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate and aspartate residues on target proteins (PubMed:18851833, PubMed:23332125, PubMed:23474714, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:18851833). Catalyzes mono-ADP-ribosylation of GSK3B, leading to negatively regulate GSK3B kinase activity (PubMed:23332125). Involved in translesion DNA synthesis in response to DNA damage via its interaction with PCNA (PubMed:24695737).

Drugs associated with PARP10

OUL243

Target

PARP10 x PARP11 x PARP14 x PARP15

Mechanism

PARP10 inhibitors [+3]

Active Org.

University of Oulu

Originator Org.

University of Oulu

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

OUL-232

Target

PARP10 x PARP12

Mechanism

PARP10 inhibitors [+1]

Active Org.

University of Oulu [+1]

Originator Org.

University of Perugia [+1]

Active Indication-

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PARP10

100 Translational Medicine associated with PARP10

0 Patents (Medical) associated with PARP10

Literatures (Medical) associated with PARP10

01 Aug 2024·Life Science Alliance

K48- and K63-linked ubiquitin chain interactome reveals branch- and length-specific ubiquitin interactors

Article

Author: Mertins, Philipp ; Pluska, Lukas ; Popp, Oliver ; Sommer, Thomas ; Lambert, Mahil ; Lenz, Christopher ; Dötsch, Volker ; Waltho, Anita

The ubiquitin (Ub) code denotes the complex Ub architectures, including Ub chains of different lengths, linkage types, and linkage combinations, which enable ubiquitination to control a wide range of protein fates. Although many linkage-specific interactors have been described, how interactors are able to decode more complex architectures is not fully understood. We conducted a Ub interactor screen, in humans and yeast, using Ub chains of varying lengths, as well as homotypic and heterotypic branched chains of the two most abundant linkage types—lysine 48–linked (K48) and lysine 63–linked (K63) Ub. We identified some of the first K48/K63-linked branch-specific Ub interactors, including histone ADP-ribosyltransferase PARP10/ARTD10, E3 ligase UBR4, and huntingtin-interacting protein HIP1. Furthermore, we revealed the importance of chain length by identifying interactors with a preference for Ub3 over Ub2 chains, including Ub-directed endoprotease DDI2, autophagy receptor CCDC50, and p97 adaptor FAF1. Crucially, we compared datasets collected using two common deubiquitinase inhibitors—chloroacetamide and N-ethylmaleimide. This revealed inhibitor-dependent interactors, highlighting the importance of inhibitor consideration during pulldown studies. This dataset is a key resource for understanding how the Ub code is read.

01 May 2024·Anticancer Research

Effect of MYC and PARP Inhibitors in Ovarian Cancer Using anIn VitroModel

Article

Author: Morea, Alessandro ; Storlazzi, Clelia Tiziana ; Tosi, Sabrina ; Sisu, Cristina ; Saravi, Sayeh ; Karteris, Emmanouil ; Hall, Marcia

BACKGROUND/AIMThe 8q24 chromosomal region, which contains the MYC and PVT1 candidate oncogenes, is amplified in carcinomas. Both genes have been involved in the etiopathogenesis of ovarian cancer (OC). In this study, we used an in vitro OC model with a known 8q24 copy number increase and in silico tools to investigate the expression of MYC/PVT1 loci and copy number variation in OC. We also assessed the effects of rucaparib (a PARP inhibitor) in the presence or absence of 10058F4 (a MYC inhibitor) on the expression of MYC/linear PVT1/circular PVT1.MATERIALS AND METHODSTissue culture, chromosome preparation, RNA extraction, RT-qPCR, FISH, and wound healing assays were employed. OncoDB, cBioportal, UALKAN, and ROC Plotter in silico tools were also utilized.RESULTSAlthough PVT1 and MYC expression levels remained unaltered in OC, putative copy number alterations across all cancers showed a marked difference between the two genes, particularly in gain and amplification for MYC. PVT1 expression demonstrated prognostic value for the treatment of patients with serous and endometrioid OC. Both genes correlated with PARP10, FAM83H, and DEPTOR. The use of rucaparib in the presence or absence of the MYC inhibitor (10058F4) in vitro, led to a significant down-regulation in the expression of MYC, linear, and circular PVT1.CONCLUSIONOur data provide a novel insight into the potential interactions of MYC and PVT1 with other genes. Moreover, we identified a new PARP inhibition mechanism down-regulating MYC, as well as the linear and circular PVT1 transcripts. Future work should expand on clinical studies to better understand the prognostic role of PVT1 in OC.

01 Apr 2024·Phenomics

Identification of Poly(ADP-ribose) Polymerase 9 (PARP9) as a Potent Suppressor for Mycobacterium tuberculosis Infection

Article

Author: Wu, Jiaxue ; Zhu, Zhenyu ; Zhao, Qi ; Weng, Shufeng ; Xu, Ying ; Zheng, Fen

ADP-ribosylation is a reversible and dynamic post-translational modification mediated by ADP-ribosyltransferases (ARTs). Poly(ADP-ribose) polymerases (PARPs) are an important family of human ARTs. ADP-ribosylation and PARPs have crucial functions in host-pathogen interaction, especially in viral infections. However, the functions and potential molecular mechanisms of ADP-ribosylation and PARPs in Mycobacterium infection remain unknown. In this study, bioinformatics analysis revealed significantly changed expression levels of several PARPs in tuberculosis patients compared to healthy individuals. Moreover, the expression levels of these PARPs returned to normal following tuberculosis treatment. Then, the changes in the expression levels of PARPs during Mycobacterium infection were validated in Tohoku Hospital Pediatrics-1 (THP1)-induced differentiated macrophages infected with Mycobacterium model strains bacillus Calmette-Guérin (BCG) and in human lung adenocarcinoma A549 cells infected with Mycobacterium smegmatis (Ms), respectively. The mRNA levels of PARP9, PARP10, PARP12, and PARP14 were most significantly increased during infection, with corresponding increases in protein levels, indicating the possible biological functions of these PARPs during Mycobacterium infection. In addition, the biological function of host PARP9 in Mycobacterium infection was further studied. PARP9 deficiency significantly increased the infection efficiency and intracellular proliferation ability of Ms, which was reversed by the reconstruction of PARP9. Collectively, this study updates the understanding of changes in PARP expression during Mycobacterium infection and provides evidence supporting PARP9 as a potent suppressor for Mycobacterium infection.Supplementary InformationThe online version contains supplementary material available at 10.1007/s43657-023-00112-2.

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