title: Novel function of the unique N-terminal region of RUNX1c in B cell growth regulation.
abstract: RUNX family proteins are expressed from alternate promoters, giving rise to different N-terminal forms, but the functional difference of these isoforms is not understood. Here, we show that growth of a human B lymphoblastoid cell line infected with Epstein-Barr virus is inhibited by RUNX1c but not by RUNX1b. This gives a novel functional assay for the unique N-terminus of RUNX1c, and amino acids of RUNX1c required for the effect have been identified. Primary resting B cells contain RUNX1c, consistent with the growth inhibitory effect in B cells. The oncogene TEL-RUNX1 lacks the N-terminus of RUNX1c because of the TEL fusion and does not inhibit B cell growth. Mouse Runx1c lacks some of the sequences required for human RUNX1c to inhibit B cell growth, indicating that this aspect of human B cell growth control may differ in mice. Remarkably, a cell-penetrating peptide containing the N-terminal sequence of RUNX1c specifically antagonizes the growth inhibitory effect in B lymphoblastoid cells and might be used to modulate the function of human RUNX1c.
authors.affiliation: Section of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
authors.forename: Gareth
authors.initials: G
authors.lastname: Brady
authors.forename: Claudio
authors.initials: C
authors.lastname: Elgueta Karstegl
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Farrell
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D050676:Core Binding Factor Alpha 2 Subunit / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006801:Humans; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; D015514:Oncogene Proteins, Fusion; D010455:Peptides; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; C488373:TEL-RUNX1 fusion protein, human; D004247:DNA