The kinetics of cell proliferation in tumours depends on the balance between cellular proliferation and the rate of deletion, which in part occurs by apoptosis.
The final common cascade for apoptosis is through a series of self-activating proteases known as caspases. Activation of caspases occurs through two pathways, one mitochondrial and a second known as the extrinsic pathway.
The mitochondrial pathway involves the release of pro-apoptotic proteins from mitochondria. bcl-2 and bcl-xL suppress apoptosis while BAX and Bak promote apoptosis.
The extrinsic pathway is stimulated by extracellular factors such as tumour necrosis factor (TNF) binding to cell membrane receptors. The nuclear factor NF-kB protects from apoptotic stimuli including TNF-a, chemotherapy and radiotherapy, by releasing inhibitor of apoptosis proteins. To date, six such proteins have been identified; XIAP, cIAP1, cIAP2, NAIP and survivin). cIAP2 is known to be involved in chromosomal translocations in lymphomas, particularly MALT lymphomas.
References
This page last revised 13.5.2003.
©SMUHT/PW Bishop