title: Phospho-dependent protein recognition motifs contained in C/EBP family of transcription factors: in silico studies.
abstract: CCAAT/enhancer-binding proteins (C/EBPs) are transcriptional regulators implicated in cell proliferation, differentiation, survival, and tumorigenesis. Their biological activities require interactions with several protein partners. This report presents insights from in silico analysis aimed at identifying phosphorylation-dependent protein recognition motifs in C/EBPs. (1) All C/EBP variants contain intrinsically disordered Ser/Thr- and Pro-rich segments with potential docking sites for WW and Polo-box domains of prolyl isomerase Pin1 and Polo-like kinases (Plks), respectively. (2) Consensus phosphorylation sequences for Plks are located in a highly conserved region of transactivation domains, suggesting that Plks might modulate transcriptional activities of C/EBPs in a cell cycle-dependent manner. (3) Phosphorylation at these positions, as well as at conserved Ser in the extended basic region, would create phosphoserine-containing motifs (pSXXF/Y/I/L), which could be recognized by BRCT repeats containing proteins such as the PAX-transactivation-domain-interacting protein (PTIP), and the breast cancer-associated protein (BRCA1). Proteins containing BRCT domains serve as scaffolds, mediating protein-protein interactions and formation of functional multiprotein complexes involved in DNA repair and cell cycle control. These findings add a new perspective to studies aimed at elucidation of molecular mechanisms underlying the diverse functions of C/EBPs.
authors.affiliation: Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Maryland 21702-1201, USA. millerm@ncifcrf.gov
authors.forename: Maria
authors.initials: M
authors.lastname: Miller
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D010766:Phosphorylation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D014157:Transcription Factors; D012694:Serine; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase