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 FunctionalityProtein 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

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

http://www.reading.ac.uk/nitricoxide/intro/apoptosis/mito2.jpgApoptosis Pathway

http://openi.nlm.nih.gov/detailedresult.php?img=2132464_JCB.amling5g&req=4

• Viable, but smaller• Half die by 6 weeks• Smaller kidneys• Skeletal

development• Immune failure

Bcl-2 Knockout Mice

https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcTkoz4iPsXeDUTi1dbV1wzIQsD8sDB7HqkRJaxih9U4UWe9Cusd-A

Non-Hodgkin

Lymphoma

http://www.sciencedirect.com/science/article/pii/S0167488903001885

Bcl-2 Translocations Found in Cancer

http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/lymphoma_htmlcourse/page3

Overexpression of Bcl-2 on the Outer Membrane of Mitochondria

Inhibiting Bcl-2

http://www.cancer.gov/images/targetedtherapies/lymphoma/m4s3c_1.jpg

http://www.cancer.gov/PublishedContent/Images/images/targetedtherapies/lymphoma/m4s3c_3.jpg

Potential Therapeutic Undergoing Clinical Trials

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