RT Book, Section
A1 Rudin, Charles M.
A1 Thompson, Craig B.
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181413559
T1 Apoptosis and Cancer
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181413559
RD 2024/04/19
AB Apoptosis  is  a  descriptive  term  for  the  phenotype  of  cells  undergoing  programmed  cell  death.  Apoptosis  is  a  critical  component  of  development  and  homeostasis  in  multicellular  eukaryotic  organisms.  Apoptotic  cell  death  can  be  distinguished  from  necrotic  cell  death  by  several  criteria,  including  characteristic  morphology  and  a  minimal  inflammatory  reaction.The  Bcl-2  family  of  proteins  plays  a  central  role  in  apoptotic  control  and  is  conserved  evolutionarily.  The  realization  that  Bcl-2  functions  to  prevent  apoptosis  defined  a  new  category  of  oncogene:  the  antiapoptotic  gene.  Apoptotic  regulation  is  dependent  on  the  relative  balance  of  opposing  Bcl-2  family  members.  Those  family  members  may  function  by  regulating  homeostasis  between  key  intracellular  organelles  and  the  cytoplasm.The  caspases  are  evolutionarily  conserved  proteases  that  function  as  important  mediators  of  apoptosis.  Control  of  caspase  activity  is  dependent  on  proteolytic  processing  of  cytoplasmic  proenzymes.  Some  of  these  proteases  have  autocatalytic  potential.  The  critical  downstream  targets  of  caspase  family  proteolysis  have  not  been  fully  defined.Many  cell  surface  receptors,  including  the  tumor  necrosis  factor  receptor  (TNFR)  family,  have  been  shown  to  modify  the  apoptotic  sensitivity  of  cells.  Different  members  of  the  TNFR  family  can  promote  or  inhibit  apoptosis.  An  apoptotic  signaling  pathway  from  some  of  these  receptors  has  been  traced  by  direct  protein–protein  interaction  from  receptor  engagement  to  caspase  activation.Cellular  and  viral  oncogenes  that  stimulate  proliferation  are  strong  inducers  of  apoptosis.  This  induction  is  probably  dependent  on  cell  cycle  checkpoints  (tumor  suppressor  gene  products)  that  detect  abnormally  replicating  cells  and  trigger  apoptosis.  Inhibition  of  apoptosis  therefore  is  frequently  an  essential  step  in  the  process  of  oncogenesis.Anticancer  therapies  induce  apoptosis  in  sensitive  cells.  Inhibition  of  apoptosis  is  a  major  mechanism  of  chemotherapeutic  resistance.  Chemotherapy  may  accelerate  the  mutagenesis  rate  and  promote  aneuploidy  of  tumors  in  which  apoptosis  has  been  suppressed.  New  therapies  directed  at  modifying  apoptotic  signaling  pathways  may  be  helpful  in  circumventing  these  problems.