Phosphorylation of the RB C-terminus regulates condensin II release from chromatin

• Published in: The Journal of biological chemistry Vol. 296; p. 100108
• Main Authors: Kim, Seung J., MacDonald, James I., Dick, Frederick A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2021; American Society for Biochemistry and Molecular Biology
• Subjects: Adenosine Triphosphatases - metabolism; Chromatin - metabolism; chromatin structure; DNA-Binding Proteins - metabolism; Epigenesis, Genetic - genetics; Humans; Multiprotein Complexes - metabolism; Mutation - genetics; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; phosphorylation; Phosphorylation - genetics; Phosphorylation - physiology; Receptors, Antigen, T-Cell - metabolism; retinoblastoma protein; Retinoblastoma Protein - metabolism; T-cell receptor; Ext; retinoblastoma protein; TCR; GST; CDK; MAPK; p38 MAPK; T-cell receptor; RB; DSB; RBC; RBLP; HA; PVA; chromatin structure; NHEJ; phosphorylation; CA
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA120.016511

The retinoblastoma tumor 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, monophosphorylated 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.