PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65

Tiejun Zhang, Kyeong Ah Park, Yuwen Li, Hee Sun Byun, Juhee Jeon, Yoonjung Lee, Jang Hee Hong, Jin Man Kim, Song-Mei Huang, Seung-Won Choi, Seon-Hwan Kim, Kyung-Cheol Sohn, Hyunju Ro, Ji Hoon Lee, Tao Lu, George R. Stark, Han-Ming Shen, Zheng-gang Liu, Jongsun Park () and Gang Min Hur ()
Additional contact information
Tiejun Zhang: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Kyeong Ah Park: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Yuwen Li: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Hee Sun Byun: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Juhee Jeon: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Yoonjung Lee: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Jang Hee Hong: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Jin Man Kim: Research Institute for Medical Science, Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Song-Mei Huang: College of Medicine, Chungnam National University
Seung-Won Choi: College of Medicine, Chungnam National University
Seon-Hwan Kim: College of Medicine, Chungnam National University
Kyung-Cheol Sohn: College of Medicine, Chungnam National University
Hyunju Ro: College of Biosciences and Biotechnology, Chungnam National University
Ji Hoon Lee: Amherst College
Tao Lu: School of Medicine, Indiana University
George R. Stark: Lerner Research Instituite, Cleveland Clinic Foundation
Han-Ming Shen: Yong Loo Lin School of Medicine, National University of Singapore
Zheng-gang Liu: Cell and Cellular Biology Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health
Jongsun Park: Infection Signaling Network Research Center, College of Medicine, Chungnam National University
Gang Min Hur: Infection Signaling Network Research Center, College of Medicine, Chungnam National University

Nature Communications, 2013, vol. 4, issue 1, 1-13

Abstract: Abstract Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 (PHF20) maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that PHF20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In PHF20 overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between PHF20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that PHF20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies PHF20 as a novel regulator of NF-κB activation and suggests that elevated expression of PHF20 may drive constitutive NF-κB activation in some cancers.

Date: 2013
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DOI: 10.1038/ncomms3062

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