Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6

Phang Lang Chen, Daniel J. Riley, Selina Chen-Kiang, Wen Hwa Lee

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

The biological function of the retinoblastoma protein (RB) in the cell division cycle has been extensively documented, but its apparent role in differentiation remains largely unexplored. To investigate how RB is involved in differentiation, the U937 large-cell lymphoma line was induced to differentiate along a monocyte/macrophage lineage. During differentiation RB was found to interact directly through its simian virus 40 large tumor antigen (T antigen)binding domain with NF-IL6, a member of the CAAT/enhancer- binding protein (C/EBP) family of transcription factors. NF-IL6 utilizes two distinct regions to bind to the hypophosphorylated form of RB in vitro and in cells. Wild-type but not mutant RB enhanced both binding activity of NF-IL6 to its cognate DNA sequences in vitro and promoter transactivation by NF-IL6 in cells. These findings indicate a novel biochemical function of RB: it activates, by an apparent chaperone-like activity, specific transcription factors important for differentiation. This contrasts with its sequestration and inactivation of other transcription factors, such as E2F-1, which promote progression of the cell cycle. Such disparate mechanisms may help to explain the dual role of RB in cell differentiation and the cell division cycle.

Original languageEnglish (US)
Pages (from-to)465-469
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number1
DOIs
StatePublished - Jan 9 1996

    Fingerprint

Keywords

  • CAAT
  • cell division
  • differentiation
  • enhancer-binding protein
  • tumor suppressor

ASJC Scopus subject areas

  • General

Cite this