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Poly(ADP-ribose) polymerase family member 4 (PARP4)

Target: PARP4
Molecular classification: Enzyme (ADP-ribosyltransferase), Vault complex protein (part of cytoplasmic ribonucleoprotein organelle), Mono-ADP-ribosyltransferase (MARylation rather than poly-ADP-ribosylation)

Overview

Poly(ADP-ribose) polymerase family member 4 (PARP4) is a large, catalytically active mono-ADP-ribosyltransferase and a component of the vault ribonucleoprotein organelle. While homologous to PARP1, PARP4 lacks the DNA-binding domains and primarily carries out mono-ADP-ribosylation. PARP4 is involved in the assembly and function of the vault complex, which plays roles in multidrug resistance and potentially modulates cancer risk. PARP4's enzyme activity, structural domains (BRCT, WGR, CAT), and protein interactions suggest possible involvement in DNA repair and tumor suppression, although its full biological function remains incompletely understood. The association with multidrug resistance and possible tumor suppressive properties make PARP4 a candidate, though not well-established, target in cancer therapeutics.

Other names: Protein mono-ADP-ribosyltransferase PARP4ADPRTL1KIAA0177PARPLARTD4PH5PPARP-4VPARPVAULT3p193VWA5C193 kDa vault proteinADP-ribosyltransferase diphtheria toxin-like 4Vault poly(ADP-ribose) polymeraseVault protein, 193 kDavon Willebrand factor A domain containing 5CPoly [ADP-ribose] polymerase 4

Mechanism of action

Enzyme inhibition (blocking mono-ADP-ribosylation activity); Inhibition of vault-associated drug resistance (via vault complex protein disruption)

Biological functions

Mono-ADP-ribosylation (catalyzes protein modification using NAD(+))Assembly of vault ribonucleoprotein complexes (interaction with major vault protein, vault RNA)Potential role in DNA repair pathways (contains BRCT domain, homologous to PARP1)Putative tumor suppressor activity (loss increases carcinogen-induced colon cancer in mice)Protein-protein interaction within vault complex

Disease associations

Cancer (colon cancer, pulmonary blastoma, Cowden syndrome; implicated in multidrug resistance and tumorigenesis)Multidrug resistance (via vault complex in ovarian cancer models)Other: Suggested, but not established, involvement in DNA repair and cell survival pathways

Safety considerations

Unclear toxicity profile (few drugs directly target PARP4; safety of PARP4 inhibition not fully established)Potential for off-target effects in vault complex or related vault proteinsPossible cancer-type dependent effects (tumor suppressive in colon, but not in lung)

Interacting drugs

AEP07 (PARP4-specific inhibitor; experimental)

3 more in the full profile.

Biomarkers

PARP4 mRNA/protein expression may correlate with drug resistance and disease status in cancer, especially ovarian cancerDNA methylation status of PARP4 promoter (potential role in cancer risk/response)

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