Abstract
Adult stem cells must limit their rate of protein synthesis, but the underlying mechanisms remain largely unexplored. Differences in protein synthesis among hematopoietic stem cells (HSCs) and progenitor cells did not correlate with differences in proteasome activity, total RNA content, mRNA content, or cell division rate. However, adult HSCs had more hypophosphorylated eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP2 as compared with most other hematopoietic progenitors. Deficiency for 4E-BP1 and 4E-BP2 significantly increased global protein synthesis in HSCs, but not in other hematopoietic progenitors, and impaired their reconstituting activity, identifying a mechanism that promotes HSC maintenance by attenuating protein synthesis.
Highlights
Adult hematopoietic stem cell (HSC) maintenance depends on these cells making less protein per hour as compared with other hematopoietic progenitors (Signer et al 2014)
Phosphorylated eukaryotic initiation factor 2α inhibits translation initiation and is part of the mechanism that limits protein synthesis in some stem cells. eIF2α can be phosphorylated under steady-state circumstances, phosphorylation is increased by a wide range of stresses, including unfolded protein responses (Wek et al 2006)
EIF2α function may vary among stem cells, as HSCs express relatively low levels of phosphorylated eIF2α (Signer et al 2014), and activation of the unfolded protein response can be deleterious to individual HSCs
Summary
Adult hematopoietic stem cell (HSC) maintenance depends on these cells making less protein per hour as compared with other hematopoietic progenitors (Signer et al 2014). Ribosome biogenesis limits protein synthesis in some stem cells. EIF2α function may vary among stem cells, as HSCs express relatively low levels of phosphorylated eIF2α (Signer et al 2014), and activation of the unfolded protein response can be deleterious to individual HSCs (van Galen et al 2014).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
