New insights in the role of Bcl-2 Bcl-2 and the endoplasmic reticulum.
The oncogenic protein Bcl-2 which is expressed in membranes of different subcellular organelles protects cells from apoptosis induced by endogenic stimuli. Most of the results published so far emphasise the importance of Bcl-2 at the mitochondria. Several recent observations suggest a role of Bcl-2 at the endoplasmic reticulum (ER). Bcl-2 located at the ER was shown to interfere with apoptosis induction by Bax, ceramides, ionising radiation, serum withdrawal and c-myc expression. Although the detailed functions of Bcl-2 at the ER remain elusive, several speculative mechanisms may be supposed. For instance, Bcl-2 at the ER may regulate calcium fluxes between the ER and the mitochondria. In addition, Bcl-2 is able to interact with the endoplasmic protein Bap31 thus avoiding caspase activation at the ER. Bcl-2 may also abrogate the function of ER located pro-apoptotic Bcl-2 like proteins by heterodimerization. Current data on the function of Bcl-2 at the ER, its role for the modulation of calcium fluxes and its influence on caspase activation at the ER are reviewed.
Department of Radiation Oncology, University of Tuebingen, Hoppe-Seyler Str. 3, D-72076 Tuebingen, Germany.
J
J
Rudner
V
V
Jendrossek
C
C
Belka
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; D002118:Calcium