Summary
Murine ES cells can be maintained as a pluripotent, self-renewing population by LIF/STAT3-dependent signaling. The downstream effectors of this pathway have not been previously defined. In this report, we identify a key target of the LIF self-renewal pathway by showing that STAT3 directly regulates the expression of the Myc transcription factor. Murine ES cells express elevated levels of Myc and following LIF withdrawal, Myc mRNA levels collapse and Myc protein becomes phosphorylated on threonine 58 (T58), triggering its GSK3β dependent degradation. Maintained expression of stable Myc (T58A) renders self-renewal and maintenance of pluripotency independent of LIF. By contrast, expression of a dominant negative form of Myc antagonizes self-renewal and promotes differentiation. Transcriptional control by STAT3 and suppression of T58 phosphorylation are crucial for regulation of Myc activity in ES cells and therefore in promoting self-renewal. Together, our results establish a mechanism for how LIF and STAT3 regulate ES cell self-renewal and pluripotency.
Footnotes
- Accepted December 22, 2004.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Other journals from The Company of Biologists
Development presents...
Catch up on the third instalment of our new interactive webinar series, this time chaired by Development Editor Yrjö Helariutta and focusing on plant development. This week’s recorded presentations and live Q&As are available to watch for the next two weeks.
The people behind the papers – Andrew Economou and Jeremy Green
First author Andrew Economou and his former supervisor Jeremy Green, Professor of Developmental Biology at King’s College, London, talk about the story behind their new paper in Development on developmental patterning systems.
Special Issue: Imaging development, stem cells and regeneration
We are now welcoming submissions to our next Special Issue, which will focus on the innovative use of advanced imaging techniques to further our understanding of developmental and regenerative processes. The issue will be published mid-2021 and the deadline for submissions is 31 March 2021.
preLights - Finding transcriptional effectors in a sea of domains
Over on preLights, Clarice Hong discusses a new preprint by Tycko et al. on high-throughput discovery and characterization of human transcriptional effectors.
Development and COVID-19
We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.