PHF10 subunit of PBAF complex mediates transcriptional activation by MYC

Oncogene. 2021 Oct;40(42):6071-6080. doi: 10.1038/s41388-021-01994-0. Epub 2021 Aug 31.

Abstract

The PBAF complex, a member of SWI/SNF family of chromatin remodelers, plays an essential role in transcriptional regulation. We revealed a disease progression associated elevation of PHF10 subunit of PBAF in clinical melanoma samples. In melanoma cell lines, PHF10 interacts with MYC and facilitates the recruitment of PBAF complex to target gene promoters, therefore, augmenting MYC transcriptional activation of genes involved in the cell cycle progression. Depletion of either PHF10 or MYC induced G1 accumulation and a senescence-like phenotype. Our data identify PHF10 as a pro-oncogenic mechanism and an essential novel link between chromatin remodeling and MYC-dependent gene transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cellular Senescence
  • Chromatin Assembly and Disassembly
  • Disease Progression
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Sequence Analysis, RNA
  • Transcriptional Activation
  • Up-Regulation

Substances

  • Homeodomain Proteins
  • MYC protein, human
  • Neoplasm Proteins
  • PHF10 protein, human
  • Proto-Oncogene Proteins c-myc