TAILIEUCHUNG - Chapter 080. Cancer Cell Biology and Angiogenesis (Part 11)

The release of apoptosis-inducing proteins from the mitochondria is regulated by pro- and antiapoptotic members of the Bcl-2 family. Antiapoptotic members (., Bcl-2, Bcl-XL, and Mcl-1) associate with the mitochondrial outer membrane via their carboxy termini, exposing to the cytoplasm a hydrophobic binding pocket composed of Bcl-2 homology (BH) domains 1, 2, and 3 that is crucial for their activity. Perturbations of normal physiologic processes in specific cellular compartments lead to the activation of BH3-only proapoptotic family members (such as Bad, Bim, Bid, Puma, Noxa, and others) that can alter the conformation of the outer-membrane proteins Bax and Bak,. | Chapter 080. Cancer Cell Biology and Angiogenesis Part 11 The release of apoptosis-inducing proteins from the mitochondria is regulated by pro- and antiapoptotic members of the Bcl-2 family. Antiapoptotic members . Bcl-2 Bcl-XL and Mcl-1 associate with the mitochondrial outer membrane via their carboxy termini exposing to the cytoplasm a hydrophobic binding pocket composed of Bcl-2 homology BH domains 1 2 and 3 that is crucial for their activity. Perturbations of normal physiologic processes in specific cellular compartments lead to the activation of BH3-only proapoptotic family members such as Bad Bim Bid Puma Noxa and others that can alter the conformation of the outer-membrane proteins Bax and Bak which then oligomerize to form pores in the mitochondrial outer membrane resulting in cytochrome c release. If BH3-only proteins are sequestered by Bcl-2 Bcl-XL or Mcl-1 pores do not form and apoptosis-inducing proteins are not released from the mitochondrion. The relative levels of expression of antiapoptotic Bcl-2 family members compared to the levels of proapoptotic BH3-only proteins at the mitochondrial membrane determines the activation state of the intrinsic pathway. The mitochondrion must therefore be recognized not only as an organelle with vital roles in intermediary metabolism and oxidative phosphorylation but also as a central regulatory structure of the apoptotic process. The evolution of tumor cells to a more malignant phenotype requires the acquisition of genetic changes that subvert apoptosis pathways and promote cancer cell survival and resistance to anticancer therapies. However because of their deranged physiology cancer cells may be more vulnerable than normal cells to therapeutic interventions that target the apoptosis pathways that cancer cells are very dependent upon. For instance overexpression of Bcl-2 as a result of the t 14 18 translocation contributes to follicular lymphoma. Upregulation of Bcl-2 expression is also observed in prostate .

• Y học thường thức
• Cancer Cell Biology and Angiogenesis
• bệnh học và điều trị
• bài giảng bệnh học
• tài liệu y khoa
• Harrisons Internal Medicine
• medical books
• pharmacology
• epidemiologic
• Obstetrics
• anatomy
• Preventing Morbidity
• Multidisciplinary Care