PELO regulates erythroid differentiation through interaction with MYC to upregulate KLF10

FEBS J. 2024 Nov;291(21):4714-4731. doi: 10.1111/febs.17254. Epub 2024 Aug 29.

Abstract

Erythropoiesis is a multistep process of erythroid cell production that is controlled by multiple regulatory factors. Ribosome rescue factor PELO plays a crucial role in cell meiotic division and mice embryonic development. However, the function of PELO in erythroid differentiation remains unclear. Here, we showed that knockdown of PELO increased hemin-induced erythroid differentiation of K562 and HEL cells, exhibiting a higher number of benzidine-positive cells and increased mRNA levels of erythroid genes. PELO knockdown inhibited the proliferation and cell cycle progression and promoted apoptosis of K562 cells. Mechanistically, PELO could regulate the expression of KLF10 through interaction with MYC. Moreover, KLF10 knockdown also enhanced erythroid differentiation of K562 and HEL cells induced by hemin. Collectively, our results demonstrated that PELO regulates erythroid differentiation and increases KLF10 expression levels by interacting with MYC.

Keywords: KLF10; MYC; PELO; erythroid differentiation; hemoglobin.

MeSH terms

  • Apoptosis
  • Cell Differentiation*
  • Cell Proliferation
  • Early Growth Response Transcription Factors / genetics
  • Early Growth Response Transcription Factors / metabolism
  • Erythroid Cells* / cytology
  • Erythroid Cells* / metabolism
  • Erythropoiesis* / genetics
  • Hemin / metabolism
  • Hemin / pharmacology
  • Humans
  • K562 Cells
  • Kruppel-Like Transcription Factors* / genetics
  • Kruppel-Like Transcription Factors* / metabolism
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins c-myc* / metabolism
  • Up-Regulation

Substances

  • Kruppel-Like Transcription Factors
  • Proto-Oncogene Proteins c-myc
  • KLF10 protein, human
  • MYC protein, human
  • Early Growth Response Transcription Factors
  • Hemin