SMURFs regulate mesendoderm differentiation through SMAD2-dependent ubiquitination of CDK9.

SMURF1 and SMURF2 ubiquitinate CDK9, regulating SMAD2-driven transcription during mesendoderm differentiation in embryonic development.

• Why it matters: Understanding how transcriptional programs are attenuated during gastrulation is crucial for insights into developmental timing and lineage specification, yet mechanisms of transcriptional attenuation remain unclear.
• What they did: The study examined SMURF1/2's role in regulating SMAD2-dependent gene expression by analyzing their effect on CDK9 ubiquitination and degradation, revealing that loss of SMURF function stabilizes CDK9 and enhances Pol II pause release.
• The result: Findings suggest that SMURF1/2-mediated ubiquitination of CDK9 restricts morphogen-induced gene expression, ensuring proper timing of mesendoderm differentiation and developmental progression.