Top

Minireview

Split Viewer

Mol. Cells 2008; 26(4): 323-328

Published online October 31, 2008

© The Korean Society for Molecular and Cellular Biology

Proteotoxic Stress and Cell Lifespan Control

Simone Cenci, Niccolò Pengo and Roberto Sitia

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 mal-adaptive 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 difficult-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 lifespan 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 anti-cancer therapies.

Keywords aging, apoptosis, cancer, immunoglobulin, multiple myeloma, plasma cells, proteasome inhibitors, proteasome, protein synthesis, stress, ubiquitin, unfolded protein response

Article

Minireview

Mol. Cells 2008; 26(4): 323-328

Published online October 31, 2008

Copyright © The Korean Society for Molecular and Cellular Biology.

Proteotoxic Stress and Cell Lifespan Control

Simone Cenci, Niccolò Pengo and Roberto Sitia

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 mal-adaptive 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 difficult-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 lifespan 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 anti-cancer therapies.

Keywords: aging, apoptosis, cancer, immunoglobulin, multiple myeloma, plasma cells, proteasome inhibitors, proteasome, protein synthesis, stress, ubiquitin, unfolded protein response

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download