HnRNP K in PU.1-containing complexes recruited at the CD11b promoter: A distinct role in modulating granulocytic and monocytic differentiation of AML-derived cells

Ervin Nika, Federica Brugnoli, Manuela Piazzi, Elisabetta Lambertini, Silvia Grassilli, Alberto Bavelloni, Roberta Piva, Silvano Capitani, Valeria Bertagnolo

Research output: Contribution to journalArticlepeer-review

Abstract

PU.1 is essential for the differentiation of haemopoietic precursors and is strongly implicated in leukaemogenesis, yet the protein interactions that regulate its activity in different myeloid lineages are still largely unknown. In the present study, by combining fluorescent EMSA(electrophoretic mobility-shift assay) with MS, we reveal the presence of hnRNP K (heterogeneous nuclear ribonucleoprotein K) in molecular complexes that PU.1 forms on the CD11b promoter during the agonist-induced maturation of AML (acute myeloid leukaemia)-derived cells along both the granulocytic and the monocytic lineages. Although hnRNP K and PU.1 act synergistically during granulocytic differentiation, hnRNP K seems to have a negative effect on PU.1 activity during monocytic maturation. Since hnRNP K acts as a docking platform, integrating signal transduction pathways to nucleic aciddirected processes, it may assist PU.1 in activating or repressing transcription by recruiting lineage-specific components of the transcription machinery. It is therefore possible that hnRNP K plays a key role in the mechanisms underlying the specific targeting of protein-protein interactions identified as mediators of transcriptional activation or repression and may be responsible for the block of haemopoietic differentiation.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalBiochemical Journal
Volume463
Issue number1
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Acute myeloid leukaemia
  • All-trans-retinoic acid (ATRA)
  • CD11b
  • Differentiation
  • PMA
  • PU.1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Fingerprint Dive into the research topics of 'HnRNP K in PU.1-containing complexes recruited at the CD11b promoter: A distinct role in modulating granulocytic and monocytic differentiation of AML-derived cells'. Together they form a unique fingerprint.

Cite this