, Volume 24, Issue 1–2, pp 1–2 | Cite as

Cancer therapeutics based on BCL-2 functional conversion

  • Martin C. Pearce
  • Arnold C. Satterthwait
  • Xiao-kun Zhang
  • Siva Kumar KolluriEmail author

The BCL-2 protein family plays a key role in the regulation of ‘intrinsic’ apoptosis by regulating the integrity of the mitochondrial outer membrane (MOM). The BCL-2 family of proteins consists of both anti-apoptotic and pro-apoptotic members. These proteins possess one to four BCL-2 Homology (BH) domains and fall into three functional groups. The anti-apoptotic proteins include BCL-2, BCL-XLand MCL-1, which possess BH1-4 domains. The pro-apoptotic BCL-2 family members are divided into two subclasses, comprising the BH3 only proteins such as NOXA and PUMA and multi-domain proteins such as BAK and BAX which possess the BH1-3 domains. The balance between the expression of pro- and anti- death BCL-2 proteins determines the cell fate as pro-survival BCL-2 members bind and inhibit the activity of pro-death members. The BH3-only proteins are upregulated upon cellular stress such as DNA damage or oncogene activation and then bind pro-survival proteins, preventing their inhibition of BAX and...



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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Martin C. Pearce
    • 1
  • Arnold C. Satterthwait
    • 2
  • Xiao-kun Zhang
    • 2
    • 3
  • Siva Kumar Kolluri
    • 1
    • 4
    Email author
  1. 1.Cancer Research Laboratory, Department of Environmental & Molecular ToxicologyOregon State UniversityCorvallisUSA
  2. 2.Sanford Burnham Prebys Medical Discovery InstituteLa JollaUSA
  3. 3.School of Pharmaceutical SciencesXiamen UniversityXiamenChina
  4. 4.Linus Pauling InstituteOregon State UniversityCorvallisUSA

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