Vault poly(ADP-ribose) polymerase (PARP4) (PARP4)

Vault poly(ADP-ribose) polymerase (vPARP), also known as PARP4, is a 193 kDa protein that serves as a key enzymatic component of the vault ribonucleoprotein complex, the largest known cellular ribonucleoprotein (UniProt P0C6P0). Unlike the well-characterized PARP1 and PARP2 enzymes which are primarily nuclear and central to DNA damage repair, vPARP is distributed in both the cytoplasm and the nucleus (Kickhoefer et al., 1999). It catalyzes the polymerization of ADP-ribose units from NAD+ onto itself and other proteins, such as the major vault protein (MVP) (NCBI Gene ID: 143). vPARP is thought to play roles in nucleocytoplasmic transport, cellular signaling, and maintaining the structural integrity of the vault complex. In clinical oncology, vPARP is often studied in the context of multidrug resistance, as vault complexes are frequently upregulated in chemoresistant cancer cells (Schütze et al., 2005). While most current PARP inhibitors like Olaparib and Niraparib are designed to target PARP1 and PARP2, their cross-reactivity with vPARP is a factor in their overall pharmacological profile (Wahlberg et al., 2012). Research suggests that vPARP may also contribute to DNA damage response pathways, although its contribution is less pronounced than that of PARP1. Understanding the specific role of vPARP is crucial for developing next-generation PARP inhibitors with improved selectivity and reduced off-target effects.

Other names

vPARPPoly(ADP-ribose) polymerase 4ADP-ribosyltransferase diphtheria toxin-like 1ADPRTL1p193PH5P

Inhibition of poly(ADP-ribose) polymerase catalytic activity, preventing the synthesis of poly(ADP-ribose) (PAR) polymers (Wahlberg et al., 2012).