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Published on: April 27, 2019
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Embryonic Cells Redistribute SUMO1 upon Forced SUMO1 Overexpression
Andreia Lee1, Yiping Zhu2,3, Yosef Sabo4
1Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University Medical Center, Columbia University, New York, New York, USA.
Mbio
|December 5, 2019
Summary
Embryonic stem cells cannot tolerate high levels of SUMO1 protein. Surviving cells adapt by reducing free SUMO1, unlike differentiated cells, highlighting unique SUMO1 needs in early development.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- SUMOylation is a critical posttranslational modification impacting numerous cellular processes.
- SUMOylation is essential for embryonic development, as global inhibition leads to lethality.
- SUMO1 and SUMO2 are key ubiquitin-like modifiers with distinct roles.
Purpose of the Study:
- To investigate the tolerance of embryonic stem (ES) cells to SUMO1 overexpression.
- To compare the effects of SUMO1 and SUMO2 overexpression in embryonic cells.
- To elucidate the adaptive mechanisms of embryonic cells surviving SUMO1 overexpression.
Main Methods:
- Overexpression of SUMO1 and SUMO2 in murine embryonic carcinoma and ES cells.
- Analysis of SUMO1 conjugation levels and free SUMO1 in surviving clones.
- Utilizing SUMO1 mutants, substrate sponges, and deSUMOylating enzymes (SENP1) to block SUMO1 conjugation.
Main Results:
- SUMO1 overexpression was poorly tolerated in embryonic cells, with few surviving clones.
- Surviving embryonic cells showed high levels of SUMO1 conjugates and undetectable free SUMO1.
- Differentiated cells tolerated SUMO1 overexpression, unlike embryonic cells.
- SUMO2 overexpression did not induce similar toxicity in embryonic cells.
- Blocking SUMO1 conjugation restored free SUMO1 levels in surviving cells.
Conclusions:
- Embryonic cells have a low tolerance for excess SUMO1 protein accumulation due to critical substrate conjugation.
- Surviving embryonic cells adapt to SUMO1 overexpression by drastically reducing free SUMO1 levels.
- This suggests a specific requirement for precise control of free SUMO1 levels in embryonic cells for proper function and survival.
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