The 193-kD vault protein, VPARP, is a novel poly(ADP-ribose) polymerase.

Mammalian vaults are ribonucleoprotein (RNP) complexes, composed of a small ribonucleic acid and three proteins of 100, 193, and 240 kD in size. The 100-kD major vault protein (MVP) accounts for >70% of the particle mass. We have identified the 193-kD vault protein by its interaction with the MVP in ...
a yeast two-hybrid screen and confirmed its identity by peptide sequence analysis. Analysis of the protein sequence revealed a region of approximately 350 amino acids that shares 28% identity with the catalytic domain of poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein that catalyzes the formation of ADP-ribose polymers in response to DNA damage. The catalytic domain of p193 was expressed and purified from bacterial extracts. Like PARP, this domain is capable of catalyzing a poly(ADP-ribosyl)ation reaction; thus, the 193-kD protein is a new PARP. Purified vaults also contain the poly(ADP-ribosyl)ation activity, indicating that the assembled particle retains enzymatic activity. Furthermore, we show that one substrate for this vault-associated PARP activity is the MVP. Immunofluorescence and biochemical data reveal that p193 protein is not entirely associated with the vault particle, suggesting that it may interact with other protein(s). A portion of p193 is nuclear and localizes to the mitotic spindle.
Mesh Terms:
Alpha-Globulins, Amino Acid Sequence, Animals, BRCA1 Protein, COS Cells, Catalytic Domain, Cell Nucleus, Cloning, Molecular, Cytoplasm, Fibroblasts, Hela Cells, Humans, Mitotic Spindle Apparatus, Molecular Sequence Data, Molecular Weight, Peptide Fragments, Poly(ADP-ribose) Polymerases, RNA, Messenger, Sequence Homology, Amino Acid, Vault Ribonucleoprotein Particles, Yeasts
J. Cell Biol.
Date: Sep. 06, 1999
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