B cell lymphoma (Bcl)-2 is a mammalian protein family whose members govern mitochondrial membrane permeabilisation (MMP), a key event in apoptosis. The titular protein of the family was first discovered as a reciprocal gene translocation in chromosomes 14 and 18 in follicar lymphomas.
The family: Bcl-2 proteins are split into two broad sub-families, the pro-apoptotic proteins and the anti-apoptotic proteins. The members of this family share characteristic domains of homology entitled the Bcl-2 homology (BH) domains. The BH domains are known to be crucial for function, as deletion of these domains via molecular cloning effects survival/apoptosis rates. The BH domains also serve to further subdivde the pro-apoptotic group into those with several BH domains (e.g. Bax and Bak) or those proteins that have only the BH3 domain (e.g. Bid, Bim and Bad). The Bcl-2 family has a general structure that consists of a hydrophbic helix surrounded by ampipathic helices. Many members of the family have transmembrane domains. The site of action for the Bcl-2 family is mostly on the outer mitochondrial membrane (OMM). Within the mitochondria are apoptogenic factors (cytochrome c, Smac/DIABLO, Omi) that if released activate the executioners of apoptosis, the caspases. Depending on their function, once activated Bcl-2 proteins either promote the release of these factors, or keep them sequestered in the mitochondria. The exact mechanisms surrounding Bcl-2 regulated MMP have yet to be elucidated.
The protein: Bcl-2 is a anti-apoptotic protein that resides in the OMM and the membrane of the endoplasmic reticulum. Over expression of Bcl-2 is known to block cytochrome c release, possibly through the inhibition of Bax and Bak. The protein also conforms to the general structure of Bcl-2 proteins, with a transmembrane domain in its C-terminus.
The Bcl-2 Family (http://www.celldeath.de/encyclo/misc/bcl2.htm)
DNA ladders were visualized on 2% of agarose gel after the cells were treated with 50 µM HA14-1 compound at the designated time.
Lanes: 1, control; 2, 1 h of HA14-1 treatment; 3, 2 h of HA14-1 treatment; 4, 3 h of HA14-1 treatment; 5, 4 h of HA14-1 treatment; 6, preincubation with zVAD-fmk for 2 h before the treatment with HA14-1 for 4 h.
Cells were treated with Fas antibody or HA14-1 for 24 h and were analyzed for DNA ladders on 2% agarose gel.
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