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Bcl-2 and its Role in Cancer. Mitochondria in the Cell. http://micro.magnet.fsu.edu/cells/mitochondria/images/mitochondriafigure1.jpg. Cytochrome C’s Dual Functionality. Protein that carries electrons in electron transport chain between mitochondrial membranes
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Mitochondria in the Cell http://micro.magnet.fsu.edu/cells/mitochondria/images/mitochondriafigure1.jpg
Cytochrome C’s Dual Functionality Protein that carries electrons in electron transport chain between mitochondrial membranes BUT released into cytosol, triggers apoptosis http://upload.wikimedia.org/wikipedia/commons/thumb/b/ba/Cytochrome_C.png/250px-Cytochrome_C.png
Bcl-2 family – apoptosis regulators http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/lymphoma_htmlcourse/page3
http://www.reading.ac.uk/nitricoxide/intro/apoptosis/mito2.jpghttp://www.reading.ac.uk/nitricoxide/intro/apoptosis/mito2.jpg Apoptosis Pathway Stress signal (DNA damage, heat shock) Pro-apoptotic members activated Cytochrome c release via MOMP Cytochrome c complexes with ATP and Apaf-1 (enzyme) Caspase-9 activated, then forms apoptosome with previous complex Caspase cascade to apoptosis
Bcl-2 Knockout Mice • Viable, but smaller • Half die by 6 weeks • Smaller kidneys • Skeletal development • Immune failure http://openi.nlm.nih.gov/detailedresult.php?img=2132464_JCB.amling5g&req=4
Non-Hodgkin Lymphoma https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcTkoz4iPsXeDUTi1dbV1wzIQsD8sDB7HqkRJaxih9U4UWe9Cusd-A
Bcl-2 Translocations Found in Cancer http://www.sciencedirect.com/science/article/pii/S0167488903001885
Overexpression of Bcl-2 on the Outer Membrane of Mitochondria http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/lymphoma_htmlcourse/page3
Inhibiting Bcl-2 http://www.cancer.gov/images/targetedtherapies/lymphoma/m4s3c_1.jpg
Potential Therapeutic Undergoing Clinical Trials http://www.cancer.gov/PublishedContent/Images/images/targetedtherapies/lymphoma/m4s3c_3.jpg
Sources • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2132464/ • http://www.scq.ubc.ca/apoptosis/ • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220196/pdf/iep_79.pdf • http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/lymphoma_htmlcourse • http://www.sciencedirect.com/science/article/pii/S0167488903001885