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Proteasome Inhibitors as Therapy in Multiple Myeloma

  • Dharminder Chauhan
  • Dharminder Ajita
  • Dharminder Singh
  • Kenneth Anderson
Part of the Contemporary Hematology book series (CH)

Ubiquitin-Proteasome System: Constitution and Function

Normal cellular homeostasis requires balanced regulation of protein synthesis and degradation. Intracellular protein degradation occurs majorly via a multi-subunit complex called the proteasome.1, 2, 3, 4 Initial studies by Ciechanover, Hershko, and Rose demonstrated that ATP-dependent conjugation of proteins with polypeptide (ubiquitin) mediates protein degradation.5, 6, 7, 8, 9, 10, 11 The role of ubiq-uitin in cellular protein turnover was further established in later studies.6,11

Proteolysis is mediated via the 26S multi-subunit proteasome complex12, 13, 14, 15 consisting of 19S units flanking a barrel-shaped 20S proteasome core.16, 17, 18The 19S units of the 26S proteasome complex regulate entry of ubiqui-tinated proteins into the 20S core chamber. 2, 19,20 Protein ubiquitination is facilitated through several enzymatic reactions: E1 ubiquitin enzyme first activates ubiquitin and then links it to the ubiquitin-conjugating...

Keywords

Multiple Myeloma Cystic Fibrosis Transmembrane Conductance Regulator Proteasome Inhibitor Proteasomal Activity Boronic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This investigation was supported by NIH grants CA 50947, CA 78373, and CA10070; the Myeloma Research Fund; and LeBow Family Fund to Cure Myeloma.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Dharminder Chauhan
    • 1
  • Dharminder Ajita
    • 2
  • Dharminder Singh
    • 2
  • Kenneth Anderson
    • 3
  1. 1.Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Myeloma ResearchDana-Farber Cancer InstituteBostonUSA
  2. 2.Dana-Farber Cancer InstituteBostonUSA
  3. 3.Department of Medical Oncology, Dana-Farber Cancer InstituteHarvard Medical SchoolBostonUSA

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