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

TitleRetinoblastoma protein directly interacts with and activates the transcription factor NF-IL6.
Publication TypeJournal Article
Year of Publication1996
AuthorsChen PL, Riley DJ, Chen-Kiang S, Lee WH
JournalProc Natl Acad Sci U S A
Date Published1996 Jan 09
KeywordsAmino Acid Sequence, Base Sequence, CCAAT-Enhancer-Binding Proteins, Cell Differentiation, DNA-Binding Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Nuclear Proteins, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Protein Binding, Retinoblastoma Protein, Sequence Alignment, Sequence Homology, Amino Acid, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured

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.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID8552662
PubMed Central IDPMC40259
Grant ListCA58318 / CA / NCI NIH HHS / United States
EY05758 / EY / NEI NIH HHS / United States
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Related Faculty: 
Selina Chen-Kiang, Ph.D.

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