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Apoptosis, Cancer and Proteins

Apoptosis, Cancer and Proteins. ISAT 351 - 4/4/00 Q Yi Candice Roman Kenny Martin Kerri Bianchet. Apoptosis Overview.

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Apoptosis, Cancer and Proteins

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  1. Apoptosis, Cancer and Proteins ISAT 351 - 4/4/00 Q Yi Candice Roman Kenny Martin Kerri Bianchet

  2. Apoptosis Overview Apoptosis is the process by which a cell actively commits suicide. It comes from two greek words: “apo” meaning “separate from” and “ptosis” meaning “fall from.” Failure of cells to undergo apoptosis, as well as failure to regulate apoptosis, can lead to cancer and AIDS.

  3. Apoptosis Overview (continued…) The steps of apoptosis: 1. The cell forms a tight sphere and its membrane undulates, resulting in bulges called blebs. 2. The nuclear membrane breaks, and endonucleases clip chromosomes where the DNA peeks out from protective proteins. 3. The cell fragments, with enough membrane sequestering toxic cell contents to prevent inflammation at the site. 4. Finally, nearby cells consume the remains.

  4. Mutation in ICE-like Proteins • When ICE-like protein is activated, they chop other various other proteins in ways that lead to destruction of the cell. • Some cutting leads directly or indirectly to destruction of the cell’s genetic material, thereby preventing the cell from maintaining itself http://www-cacse.ucsd.edu/discovery/lo/images/bio-ice.gif

  5. Mutations in ICE-like Proteins • Mutations in this protein will inhibit apoptosis of the cell. • The protein will not be able to “chop” various other proteins and it’ll inhibit the protein from destroying the genetic material of the cell directly or indirectly. http://www.sdsc.edu/GatherScatter/GSfall96/images/molecular2.gif

  6. Mutation on FAS • Fas controls the life span of certain cells, particularly the lymphocytes. Like people, cells have a normal life span in which they grow, do their job, and then die. • The mutated Fas protein does not work well, and can't give the cells the message that it is time to die.

  7. BCL-2 in Apoptosis • Human oncogene located on chromosome 18 • Integral membrane protein • BCL-2 is an “apoptosis off” control - (repressor) • Dominant effects with respect to cancer • Mutation would lead to uncontrolled apoptosis • Encodes a mitochondrial protein that blocks programmed cell death • High amounts found in lymphoid malignancies and apoptotic tissue • High expression = low remission rates in cancer

  8. p53’s Effect on Cancer • Once cell death is diminished, other consequences of p53 loss may accelerate the tumor progression more aggressively • An intact p53 gene and accompanying protein is vital in normal cell proliferation • It either temporarily halts cell division so the cell can repair altered DNA, or sends the cell to an apoptotic death. • The p56 gene is altered in approximately 50% of all human malignancies Figure: Structural features of the p53 tumor suppressor gene. http://members.aye.net/~jfbaker/p53.html

  9. p53’s Effect on Cancer • Mutations are most common genetic changes in human cancer • p53 is a tumor suppressor gene • protective method against tumor formation • Binds to many important cellular proteins • Involved in the control of gene expression http://bioscience.org/images/p53.gif

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