p53 function and regulation in normal cells and cancer cells 생명시스템학과 종양학 실험실 강 소 미

Index Normal cells vs Cancer cells Tumor suppressor genes p53 p53 in normal cells p53 in cancer cells Summary

Difference between normal cells and cancer cells

Uncontrolled cell division

Normal cell Malignant cell Abnormal shape and size Increased mitotic activity

Normal cell Cancer cell Small, uniformly shaped nuclei Relatively large cytoplasmic volume Conformity in cell size and shape Cells arranged into discrete tissues May possess differentiated cell structures Normal presentation of cell surface markers Lower levels of dividing cells Cell tissues clearly demarcated Large, variable shaped nuclei Relatively small cytoplasmic volume Variation in cell size and shape Disorganized arrangement of cells Loss of normal specialized features Elevated expression of certain cell markers Large number of dividing cells Poorly defined tumor boundaries

About tumor suppressor genes..

Tumor suppressor genes Anti-oncogenes Genes that protect cells from one step on the path to cancer Normally act to inhibit cell proliferation and tumor development

Common human tumor suppressor genes

Mechanisms of tumor suppressor genes inactivation Deletion Point mutation Mutation followed by duplication Loss of heterozygosity DNA methylation Post-translational mechanism-binding to DNA viral onco-proteins

About p53, one of major tumor suppressor genes..

p53 Tumor suppressor genes

Major function of p53

p53 function and regulation in normal cells..

p53, the cellular gate keeper for growth and division

p53 regulates cellular redox homeostasis

p53 as an integrator of cellular stress

In normal cells, the p53 product acts at the G1→S checkpoint preventing entry into S phase if DNA is damaged

In normal cells, the p53 product stimulates Apoptosis if DNA damage cannot be repaired p53 gives an internal signal for apoptosis

Regulation of p53 in normal cells In normal cells, there are low levels of p53 because p53 is targeted for proteasomal degradation P53 is activated in response to cellular stress, such as biochemical signal, UV radiation, X-rays and toxin

Regulation of p53 in normal cells

Loss of p53 function and regulation in cancer cells..

In cancer cells, mutation occurred in p53 Mutant p53 oncogenic gain of function

Regulation of wild and mutant p53 stability in response to stress

Mutant p53 signaling in cancer cells

In cancer cells, mutant p53 cannot arrest the cell cycle

Mutant p53 cannot inhibit abnormal cell division

Summary

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