ReferenceID 182
The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription
Mol Cell
Super elongation complexes (SECs) contain two different transcription elongation factors, P-TEFb and ELL1/2, linked by the scaffolding protein AFF4 or AFF1. They stimulate the expression of both normal and disease-rela
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Record Fields
Scalar fields from the final reference record.
- Reference Id
- 182
- Evidence Id
- 16772
- Core Evidence Id
- 16772
- Source Reference Id
- 353
- Herb2 Reference Id
- HBREF000644
- Subject Paper Key
- HBIN040889_22483617
- Pubmed Id
- 22483617
- Doi
- 10.1016/j.molcel.2012.03.007
- Paper Title
- The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription
- Paper Abstract
- Super elongation complexes (SECs) contain two different transcription elongation factors, P-TEFb and ELL1/2, linked by the scaffolding protein AFF4 or AFF1. They stimulate the expression of both normal and disease-related genes, especially those of HIV or those involved in leukemogenesis. Among all SEC subunits, ELL2 is stoichiometrically limiting and uniquely regulated at the level of protein stability. Here we identify the RING domain protein Siah1, but not the homologous Siah2, as the E3 ubiquitin ligase for ELL2 polyubiquitination and proteasomal degradation. Siah1 cannot access and ubiquitinate ELL2 bound to AFF4, although, at high concentrations, it also degrades AFF4/1 to destroy SECs. Prostratin and HMBA, two well-studied activators of HIV transcription and latency, enhance ELL2 accumulation and SECs formation largely through decreasing Siah1 expression and ELL2 polyubiquitination. Given its importance in formation of SECs, the Siah1 ubiquitination pathway provides a fresh avenue for developing strategies to control disease-related transcription.
- Journal
- Mol Cell
- Publish Year
- 2012
- Experiment Subject
- hela cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- HIV
- Paper Title Cn
- Paper Title En
- The ubiquitin ligase Siah1 controls ELL2 stability and formation of super elongation complexes to modulate gene transcription
- Bilingual Status
- semi_complete