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Phosphorylation of the RB C-terminus regulates condensin II release from chromatin
- Source :
- Paediatrics Publications, The Journal of Biological Chemistry
- Publication Year :
- 2021
- Publisher :
- Scholarship@Western, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Paediatrics Publications, The Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....f9be0b63c79d03d1f4bc3942d5d930d0