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, Gang Min Hur

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Article number2062
JournalNature communications
Volume4
DOIs
StatePublished - Jun 25 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Zhang, T., Ah Park, K., Li, Y., Sun Byun, H., Jeon, J., Lee, Y., Hee Hong, J., Man Kim, J., Huang, S. M., Choi, S. W., Kim, S. H., Sohn, K. C., Ro, H., Hoon Lee, J., Lu, T., Stark, G. R., Shen, H. M., Liu, Z. G., Park, J., & Min Hur, G. (2013). PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65. Nature communications, 4, [2062]. https://doi.org/10.1038/ncomms3062