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Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP‐mediated transcription *
Author(s) -
Charles Amos,
Tang Xiaoren,
Crouch Erika,
Brody Jerome S.,
Xiao ZhiXiong Jim
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.1239
Subject(s) - transactivation , e2f , retinoblastoma protein , ccaat enhancer binding proteins , microbiology and biotechnology , transcription factor , regulation of gene expression , histone , biology , chemistry , nuclear protein , gene , transcription (linguistics) , cell cycle , biochemistry , linguistics , philosophy
The retinoblastoma protein (RB) recruits histone deacetylase (HDAC) to repress E2F‐mediated transactivation that plays a critical role in cell cycle regulation. RB is also involved in activation of expression of a number of tissue specific‐ and differentiation‐related genes. In this study, we examined the mechanism by which RB stimulated the expression of a differentiation‐related gene, the surfactant protein D (SP‐D), which plays important roles in innate host defense and the regulation of surfactant homeostasis. We demonstrated that RB specifically stimulated the activity of human SP‐D gene promoter. The RB family member, p107 but not p130, also increased SP‐D promoter activity. Activation by RB was mediated through a NF‐IL6 (C/EBPβ) binding motif in the human SP‐D promoter, and this sequence specifically bound to C/EBPα, C/EBPβ, and C/EBPδ. RB formed stable complexes with all three C/EBP family members. RB small pocket (amino acid residues 379–792), but not the C‐pocket (amino acid residues 792–928), was necessary and sufficient for its interaction with C/EBP proteins. Furthermore, we demonstrated that the complexes containing RB and C/EBP proteins directly interacted with C‐EBP binding site on DNA. These findings indicate that RB plays a positive, selective, and direct role in the C/EBP‐dependent transcriptional regulation of human SP‐D expression. J. Cell. Biochem. 83: 414–425, 2001. © 2001 Wiley‐Liss, Inc.