The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death.
Each cell is under constant surveillance to maintain the integrity of its genome. Genomic lesions in a cell must be repaired before the onset of DNA replication and cell division. In the scenario that the genomic lesion is not repairable, the damaged cells are disposed in an orderly manner known as programmed cell death or apoptosis. Apoptosis and cell cycle progression are two intimately linked phenomena. Uncontrollable cell proliferation perturbs the cellular homeostasis and this can lead to malignancies, as well as organ dysfunction and developmental abnormalities. The biological pathway controlling cell fate is sequentially organized at the molecular level. Recent studies have made important contributions in advancing our knowledge of the mechanisms of cell cycle control and apoptosis regulation. A oncogene-derived protein, Bcl2, confers negative control in the pathway of cellular suicide machinery. A Bcl2-homologous protein, Bax, promotes cell death by competing with Bcl2. While Bax-Bax homodimers act as apoptosis inducers, Bcl2-Bax heterodimer formation evokes a survival signal for the cells. Both Bcl2 and Bax are transcriptional targets for the tumour suppressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. In all, the coordinate performance of these molecules is crucial for controlling life and death of a cell.
Basu
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Rammelkamp Center for Education & Research, Department of Pharmacology, MetroHealth/Case Western Reserve University, Cleveland, OH 44109-1998, USA.
Haldar
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D000818:Animals; D001940:Breast / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D010053:Ovary / Q000378:metabolism; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D013737:Testis / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014599:Uterus / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein