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

PU.1 is essential for the differentiation of haematopoietic precursors and is strongly implicated in leukemogenesis, yet the protein interactions that regulate its activity in different myeloid lineages are still largely unknown. Here, by combining fluorescent electrophoretic mobility shift assay (EMSA) with mass spectrometry, we reveal the presence of hnRNP K in molecular complexes that PU.1 forms on the CD11b promoter during the agonist-induced maturation of AML-derived cells along both the granulocytic and the monocytic lineages. WhilehnRNP 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 acid-directed processes, it mayassist 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 responsible for the block of haematopoietic differentiation.

Source: BJ Gene - July 9, 2014 Category: Biochemistry Authors: E Nika, F Brugnoli, M Piazzi, E Lambertini, S Grassilli, A Bavelloni, R Piva, S Capitani, V Bertagnolo Tags: BJ Gene Source Type: research