Proteotoxic stress and cell lifespan control

Simone Cenci, Niccolò Pengo, Roberto Sitia

Research output: Contribution to journalArticlepeer-review

Abstract

Eukaryotic cells continuously integrate intrinsic and extrinsic signals to adapt to the environment. When exposed to stressful conditions, cells activate compartment-specific adaptive responses. If these are insufficient, apoptosis ensues as an organismal defense line. The mechanisms that sense stress and set the transition from adaptive to maladaptive responses, activating apoptotic programs, are the subject of intense studies, also for their potential impact in cancer and degenerative disorders. In the former case, one would aim at lowering the threshold, in-the latter instead to increase it. Protein synthesis, consuming energy for anabolic processes as well as for byproducts disposal, can be a significant source of stress, particularly when difficutt-to-fold proteins are produced. Recent work from our and other laboratories on the differentiation of antibody secreting cells, revealed a regulatory circuit that integrates protein synthesis, secretion and degradation (proteostasis), into cell life-span determination. The apoptotic elimination - after an industrious, yet short lifetime - of terminal immune effectors is crucial to maintain immune homeostasis. Linking proteostasis to cell death, this paradigm might prove useful for biotechnological purposes, and the design of novel anticancer therapies.

Original languageEnglish
Pages (from-to)323-328
Number of pages6
JournalMolecules and Cells
Volume26
Issue number4
Publication statusPublished - Oct 31 2008

Keywords

  • Aging
  • Apoptosis
  • Cancer
  • Immunoglobulin
  • Multiple myeloma
  • Plasma cells
  • Proteasome
  • Proteasome inhibitors
  • Protein synthesis
  • Stress ubiquitin
  • Unfolded protein response

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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