Improvement of protein production

C - Chemistry – Metallurgy – 12 – N

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C12N 15/67 (2006.01)

Patent

CA 2677925

The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphateat Golgi membranes and reduces ceramide transfer activity,identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKDdependentprotein cargo transport to the plasma membrane. The interdependence of PKDand CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.

L'invention concerne le domaine technologique de la production de protéines et de la culture cellulaire. La protéine CERT est identifiée comme nouveau substrat de la PKD in vivo. La phosphorylation sur la sérine 132 par la PKD réduit l'affinité de la CERT avec sa cible lipidique phosphatidylinositol 4-phosphate au niveau des membranes de Golgi et réduit l'activité de transfert de céramide, identifiant la PKD comme un régulateur de l'homéostasie lipidique. La présente invention démontre que la CERT est également essentielle pour l'activation de la PKD et le transport de protéines dépendantes de la PKD vers la membrane plasmatique. L'interdépendance de la PKD et de la CERT est ainsi essentielle pour le maintien de l'intégrité des membranes de Golgi et du transport des sécrétions.

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