LIFE/DEATH SIGNALS: Signalling for death and survival in neurons

• Research unit: EU RFP
• Project number: 00.0074

Key words (English)

Death and survival in neurons

Alternative project number (English)

EU project number: QL-G3-1999-00602

Research programs (English)

EU-programme: 5. Frame Research Programme - 1.1.8 Generic R&D activities

Short description (English)

See abstract

Further information (English)

Full name of research-institution/enterprise:
Serono International SA
Serono Pharmaceutical Research Institute

Partners and International Organizations (English)

Coordinator: Inst. Nat. de la Santé et de la Recherche Médicale (F)

Abstract (English)

Bid is a proapoptotic member of the Bcl-2 family which plays a major role in Fas-mediated apoptosis of a certain type of cells. In these so-called type II cells, following cleavage by caspase 8, the C-terminus of Bid translocates to mitochondria and triggers the release of apoptogenic factors. We have shown that Bid is a phosphoprotein. Serines 61 and 64 as well as threonine 58 were identified as the the main phosphorylation sites of mouse Bid. We have developed a phospho-specific anti-Bid antibody recognizing specifically Bid phosphorylated on serines 61 and 64. We have also identified casein kinase I and II (CKI and CKII) as the kinases responsible for Bid phosphorylation in various cell types. Inhibition of CKI and CKII accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the kinases delayed cell death. When phosphorylated, Bid was insensitive to caspase 8 in vitro. Moreover, a mutant of Bid that cannot be phosphorylated was found to be more toxic than wild type Bid. Together, these data indicate that phosphorylation of Bid represents a new mechanism whereby cells control apoptosis and could prefigure a general regulatory mechanism of protein cleavage by caspases.
These results have been published in Mol Cell, 8 page 601-611.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 00.0074