CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that all contain a highly conserved, basic-leucine zipper domain at the C-terminus that is involved in dimerization and DNA binding. At least six members of the family have been isolated and characterized to date (C/EBPα—C/EBPζ), with further diversity produced by the generation of different sized polypeptides, predominantly by differential use of translation initiation sites, and extensive protein—protein interactions both within the family and with other transcription factors. The function of the C/EBPs has recently been investigated by a number of approaches, including studies on mice that lack specific members, and has identified pivotal roles of the family in the control of cellular proliferation and differentiation, metabolism, inflammation and numerous other responses, particularly in hepatocytes, adipocytes and haematopoietic cells. The expression of the C/EBPs is regulated at multiple levels during several physiological and pathophysiological conditions through the action of a range of factors, including hormones, mitogens, cytokines, nutrients and certain toxins. The mechanisms through which the C/EBP members are regulated during such conditions have also been the focus of several recent studies and have revealed an immense complexity with the potential existence of cell/tissue- and species-specific differences. This review deals with the structure, biological function and the regulation of the C/EBP family.
- transcription factors
Abbreviations used: AP, activator protein; APR, acute-phase response; ATF, activating transcription factor; BAT, brown adipose tissue; BTEB, basic transcription element-binding protein; bZIP, basic-leucine zipper; C/EBP, CCAAT/enhancer-binding protein; CRE, cAMP-responsive element; CREB, cAMP-response-element-binding protein; CUP, C/EBP undifferentiated protein; EGF, epidermal growth factor; ER, endoplasmic reticulum; G-CSF, granulocyte colony stimulating factor; GM-CSF, granulocyte—macrophage colony stimulating factor; GRP, glucose-regulated protein; IFN-γ, interferon-γ; IL, interleukin; LAP, liver activating protein; LIP, liver inhibitory protein; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein-1; M-CSF, macrophage colony stimulating factor; mim-1, myb-induced myeloid protein-1; MIP, macrophage inflammatory protein; mTOR, mammalian target of rapamycin; NF, nuclear factor; NGF, nerve growth factor; PDGF, platelet-derived growth factor; PEPCK, phosphoenolpyruvate carboxykinase; PI 3-kinase, phosphoinositide 3-kinase; PKA, protein kinase A; PKC, protein kinase C; PPAR, peroxisome-proliferator-activated receptor; Rb, retinoblastoma; RSK, ribosomal protein S-6 kinase; Runx, Runt domain factor; STAT, signal transducer and activator of transcription; TGF, transforming growth factor; TLS, translocated in liposarcoma; TNFα, tumour necrosis factor-α; TPA, tumour promoter activators; USF, upstream stimulating factor; uORF, upstream open reading frame; UVC, UV light band C; VIP, vasoactive intestinal peptide; WAT, white adipose tissue.
- The Biochemical Society, London ©2002