Characterization of human phosphodiesterase 12 and identification of a novel 2'-5' oligoadenylate nuclease - The ectonucleotide pyrophosphatase/phosphodiesterase 1

Bidragets oversatte titel: Karakterisering af human phosphodiesterase 12 og identifikation af en ny 2'-5' oligoadenylat nuklease - Ectonukleotid pyrophosphatase/phosphodiesterase 1

Jesper B Poulsen, Kasper Røjkjær Andersen, Karina H Kjær, Anna L Vestergaard, Just Justesen, Pia Møller Martensen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

The vertebrate 2-5A system is part of the innate immune response and central to cellular antiviral activities. Upon activation by viral double-stranded RNA, 5'-triphosphorylated, 2'-5'-linked oligoadenylate polyribonucleotides (2-5As) are synthesized by one of several 2'-5' oligoadenylate synthetases. The 2-5As bind and activate RNase L, an unspecific endoribonuclease, resulting in viral and cellular RNA decay. Given that most endogenous RNAs are degraded by RNase L, continued enzyme activity will eventually lead to cell growth arrest and cell death. This is averted, when 2-5As and their 5'-dephosphorylated forms, the so-called 2-5A core molecules, are cleaved and thus inactivated by 2'-5'-specific nuclease(s), e.g. phosphodiesterase 12, thereby turning RNase L into its latent form. In this study, we have characterized the human phosphodiesterase 12 in vitro focusing on its ability to degrade 2-5As and 2-5A core molecules. We have found that the enzyme activity is distributive and is influenced by temperature, pH and divalent cations. This allowed us to determine V(max) and K(m) kinetic parameters for the enzyme. We have also identified a novel 2'-5'-oligoadenylate nuclease; the human plasma membrane-bound ectonucleotide pyrophosphatase/phosphodiesterase 1, suggesting that 2-5A catabolism may be a multienzyme-regulated process.
Bidragets oversatte titelKarakterisering af human phosphodiesterase 12 og identifikation af en ny 2'-5' oligoadenylat nuklease - Ectonukleotid pyrophosphatase/phosphodiesterase 1
OriginalsprogEngelsk
TidsskriftBiochimie
Vol/bind94
Nummer5
Sider (fra-til)1098-1107
Antal sider10
ISSN0300-9084
DOI
StatusUdgivet - maj 2012

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