Protein Targeting



Apoptosis is a form of programmed cell death.
After a cell receives some insult and is damaged it attempts to self repair. If this is not successful then the cell pulls out its little gun and shoots itself. Bcl-2 regulates this decision process giving the cell extra time to repair before committing to cell death.

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We are studying several aspects of apoptosis.  One of our main goals is to understand how the different Bcl-2 family members regulate apoptosis.  The four proteins that we are studying (Bcl-2, Bcl-XL, Bax and Bak) are all targeted to membranes by a hydrophobic sequence at the carboxyl-terminus called a tail-anchor.  During our analysis of the targeting of protein with tail-anchors we came up with a way to use the tools of protein targeting to dissect the apoptosis pathways regulated by Bcl-2 family proteins.  we also discovered a novel mechanism by which intercellular adhesion is regulated during apoptosis.  We are now attempting to determine if regulation of intercellular adhesion by Bcl-2 has any role in metastasis of tumours.

The animation shown here displays the mechanism of outer membrane permeabilization of the mitochondria. It highlights the recruitment of Bax by tbid and subsequent release of cytochrome C from the mitochondria.

To identify the role of the transcription factor c-myc in apoptosis we have utilized a myc deficient rat fibroblast cell line.  In the absence of myc etoposide induces the translocation of Bax to the mitochondria, however it does not trigger cytochrome c release