Phosphorylation of the RB C-terminus regulates condensin II release from chromatin
| Autor: | Frederick A. Dick, James I. MacDonald, Seung J. Kim |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mutant retinoblastoma protein p38 Mitogen-Activated Protein Kinases PVA pervanadate Biochemistry Jurkat cells GST glutathione S-transferase Epigenesis Genetic RBLP RB large pocket T-cell receptor CDK cyclin-dependent kinase Adenosine Triphosphatases chromatin structure biology phosphorylation Chemistry Kinase Retinoblastoma protein Chromatin Cell biology DNA-Binding Proteins RB retinoblastoma tumor suppressor protein Mitogen-activated protein kinase NHEJ nonhomologous end joining Phosphorylation Signal transduction Research Article RBC RB C-terminus p38 mitogen-activated protein kinases Receptors Antigen T-Cell macromolecular substances p38 MAPK 03 medical and health sciences Cyclin-dependent kinase Humans DSB double-strand break Epigenetics Ext whole cell extract Molecular Biology 030102 biochemistry & molecular biology Cell Biology 030104 developmental biology TCR T-cell receptor Multiprotein Complexes Mutation CA calyculin A biology.protein MAPK mitogen-activated protein kinase HA hemagglutinin |
| Zdroj: | Paediatrics Publications The Journal of Biological Chemistry |
| Popis: | The retinoblastoma tumour suppressor protein (RB) plays an important role in biological processes such as cell cycle control, DNA damage repair, epigenetic regulation, and genome stability. The canonical model of RB regulation is that cyclin-CDKs phosphorylate, and render RB inactive in late G1/S, promoting entry into S phase. Recently, mono-phosphorylated RB species were described to have distinct cell-cycle independent functions, suggesting that a phosphorylation code dictates diversity of RB function. However, a biologically relevant, functional role of RB phosphorylation at non-CDK sites has remained elusive. Here, we investigated S838/T841 dual phosphorylation, its upstream stimulus, and downstream functional output. We found that mimicking T-cell receptor activation in Jurkat leukemia cells induced sequential activation of downstream kinases including p38 MAPK, and RB S838/T841 phosphorylation. This signaling pathway disrupts RB and condensin II interaction with chromatin. Using cells expressing a WT or S838A/T841A mutant RB fragment, we present evidence that deficiency for this phosphorylation event prevents condensin II release from chromatin. |
| Databáze: | OpenAIRE |
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