Mechanisms of protein homeostasis (proteostasis) maintain stem cell identity in mammalian pluripotent stem cells

Abstract

Protein homeostasis, or proteostasis, is essential for cell function, development, and organismal viability. The composition of the proteome is adjusted to the specific requirements of a particular cell type and status. Moreover, multiple metabolic and environmental conditions challenge the integrity of the proteome. To maintain the quality of the proteome, the proteostasis network monitors proteins from their synthesis through their degradation. Whereas somatic stem cells lose their ability to maintain proteostasis with age, immortal pluripotent stem cells exhibit a stringent proteostasis network associated with their biological function and intrinsic characteristics. Moreover, growing evidence indicates that enhanced proteostasis mechanisms play a central role in immortality and cell fate decisions of pluripotent stem cells. Here, we will review new insights into the melding fields of proteostasis and pluripotency and their implications for the understanding of organismal development and survival.

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Abbreviations

CMA:

Chaperone-mediated autophagy

ER:

Endoplasmic reticulum

HSPs:

Heat-shock chaperone proteins

HSR:

Heat-shock response

hESCs:

Human embryonic stem cells

iPSCs:

Induced pluripotent stem cells

JDPs:

J-domain proteins

mESCs:

Mouse embryonic stem cells

NSCs:

Neural stem cells

NEFs:

Nucleotide exchange factors

UPS:

Ubiquitin proteasome system

UPR:

Unfolded protein response

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (VI742/1-1 and CECAD).

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Correspondence to David Vilchez.

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Noormohammadi, A., Calculli, G., Gutierrez-Garcia, R. et al. Mechanisms of protein homeostasis (proteostasis) maintain stem cell identity in mammalian pluripotent stem cells. Cell. Mol. Life Sci. 75, 275–290 (2018). https://doi.org/10.1007/s00018-017-2602-1

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Keywords

  • Autophagy
  • Chaperones
  • Differentiation
  • Pluripotency
  • Proteostasis
  • Proteasome
  • Stress responses