Deactivation of regulatory proteins hnRNP A1 and A2 during SC-1 induced apoptosis¹

Article type: Research Article

Authors: Hermann, Ralph^a | Hensel, Frank^a | Müller, Eva-Christina^b | Keppler, Marc^a | Souto-Carneiro, Margarida^{a; **} | Brändlein, Stephanie^a | Müller-Hermelink, Hans Konrad^a | Vollmers, H. Peter^{a; *}

Affiliations: [a] Institute of Pathology, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany | [b] Max Delbrück Center for Molecular Medicine, Berlin, Germany

Correspondence: [*] Corresponding author: Institut für Pathologie, Universität Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany. Tel./Fax.: +49 931 2013898; E-mail: [email protected].

Note: [1] This project was partly supported by the Deutsche Krebshilfe e.V.

Note: [**] Current address: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract: Phosphorylation and activation of caspases play an important role in the induction of apoptosis. During tumor specific apoptosis, induced by the human monoclonal antibody SC-1, tyrosine phosphorylation and serine dephosphorylation of several proteins is observed. In this paper we describe the identification of two dephosphorylated proteins as heterogeneous nuclear ribonucleoproteins A1 and A2 (hnRNP A1, hnRNP A2). The dephosphorylation of these proteins is important for apoptosis since the amount of apoptotic cell death can be decreased by the specific serine/threonine phosphatase inhibitor okadaic acid. We also investigated the effect of serine kinase inhibitor H7 on SC-1 induced apoptosis, which leads to a dose dependent increase in apoptosis. We could also show that 24 hours after the induction of apoptosis the hnRNP A1 protein is cleaved into different cleavage products. Further, we found a decreased expression of caspase-2 in early apoptosis signalling and an overexpression 24 hours after induction of apoptosis. Our results show that the phosphorylation status of the hnRNP A1 and A2 plays a significant role in early SC-1 induced apoptosis signalling and further indicate the role of caspase activation during the apoptotic process.

Keywords: SC-1, apoptosis, hnRNP, stomach carcinoma

DOI: 10.3233/HAB-2001-10205

Journal: Human Antibodies, vol. 10, no. 2, pp. 83-90, 2001