Last update 01 Nov 2024

PARP12

Last update 01 Nov 2024

Basic Info

Synonyms

ADP-ribosyltransferase diphtheria toxin-like 12, ARTD12, FLJ22693

+ [8]

Introduction

Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.

Drugs associated with PARP12

Cpd-36

Target

PARP12 x PARP7

Mechanism

PARP-7 inhibitors [+1]

Active Org.

Chinese Academy of Medical Scciences & Peking Union Medical College

Originator Org.

Chinese Academy of Medical Scciences & Peking Union Medical College

Active Indication

Breast Cancer [+1]

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 PARP12

100 Translational Medicine associated with PARP12

0 Patents (Medical) associated with PARP12

Literatures (Medical) associated with PARP12

01 May 2024·Cellular Signalling

Deciphering the immunological and prognostic features of hepatocellular carcinoma through ADP-ribosylation–related genes analysis and identify potential therapeutic target ARFIP2

Article

Author: Hu, Bin ; Jiang, Fenfen ; Lv, Qing ; Wang, Zhiyong ; Jiang, Zhuang ; Xu, Yan

BACKGROUNDHepatocellular carcinoma is one of the most common malignancies, and its prognosis and treatment outcome cannot be accurately predicted. ADP-ribosylation (ADPR) is a post-translationa modification of proteins involved in protein trafficking and immune response. Therefore, it is necessary to explore the ADPR-related genes associated with the prognosis and therapeutic efficacy of hepatocellular carcinoma treatments.METHODSWe downloaded the data of hepatocellular carcinoma samples to identify ADPR-related genes as prognostic markers, and established a novel ADPR-related index (ADPRI) based on univariate and multivariate COX regression analyses. Patients' prognosis, clinical features, somatic variant, tumor immune microenvironment, chemotherapeutic response and immunotherapeutic response were systematically analyzed. Finally, the role of ARFIP2 in hepatocellular carcinoma cells was preliminarily explored in vitro.RESULTSThe ADPRI consisting of four ADPR related genes (ARL8B, ARFIP2, PARP12, ADPRHL1) was established to be a reliable predictor of survival in patients with hepatocellular carcinoma and was validated using external datasets. Compared with the low ADPRI group, the high ADPRI group presented higher levels of mutation frequency, immune infiltration and patients in high ADPRI group benefit more from immune checkpoint inhibitor treatment. In addition, we predicted some natural small molecule drugs as potential therapeutic targets for hepatocellular carcinoma. Finally, Knockdown of ARFIP2 inhibits the proliferation and migration of hepatocellular carcinoma cells by inducing the G1/S phase cell cycle arrest in HCC cells.CONCLUSIONSThe ADPRI can be used to accurately predict the prognosis and immunotherapeutic response of hepatocellular carcinoma patients and providing valuable insights for future precision treatment of patients with hepatocellular carcinoma.

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.

01 Mar 2024·Journal of Dental Research

P. gingivalis–Induced TLR2 Interactome Analysis Reveals Association with PARP9

Article

Author: Elgavish, S ; Nussbaum, G ; Pandi, K ; Makkawi, H ; Angabo, S ; Benyamini, H

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium strongly associated with periodontal disease. Toll-like receptor 2 (TLR2) is indispensable for the host response to P. gingivalis, but P. gingivalis escapes from immune clearance via TLR2-dependent activation of phosphoinositide-3-kinase (PI3K). To probe the TLR2-dependent escape pathway of P. gingivalis, we analyzed the TLR2 interactome induced following P. gingivalis infection or activation by a synthetic lipopeptide TLR2/1 agonist on human macrophages overexpressing TLR2. Interacting proteins were stabilized by cross-linking and then immunoprecipitated and analyzed by mass spectrometry. In total, 792 proteins were recovered and network analysis enabled mapping of the TLR2 interactome at baseline and in response to infection. The P. gingivalis infection-induced TLR2 interactome included the poly (ADP-ribose) polymerase family member mono-ADP-ribosyltransferase protein 9 (PARP9) and additional members of the PARP9 complex (DTX3L and NMI). PARP9 and its complex members are highly upregulated in macrophages exposed to P. gingivalis or to the synthetic TLR2/1 ligand Pam3Cys-Ser-(Lys)4 (PAM). Consistent with its known role in virally induced interferon production, PARP9 knockdown blocked type I interferon (IFN-I) production in response to P. gingivalis and reduced inflammatory cytokine production. We found that P. gingivalis drives signal transducer and activation of transcription (STAT) 1 (S727) phosphorylation through TLR2-PARP9, explaining PARP9’s role in the induction of IFN-I downstream of TLR2. Furthermore, PARP9 knockdown reduced PI3K activation by P. gingivalis, leading to improved macrophage bactericidal activity. In summary, PARP9 is a novel TLR2 interacting partner that enables IFN-I induction and P. gingivalis immune escape in macrophages downstream of TLR2 sensing.

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