Minireview: Pref-1: role in adipogenesis and mesenchymal cell fate.
Preadipocyte factor-1 [Pref-1; also called Dlk1 (Delta-like protein 1)] is made as an epidermal growth factor-repeat containing transmembrane protein that produces a biologically active soluble form by TNF-alpha-converting enzyme (TACE)-mediated cleavage. Soluble Pref-1 activates the MAPK kinase/ERK pathway. In adipose tissue, Pref-1 is specifically expressed in preadipocytes but not in adipocytes and thus is used as a preadipocyte marker. Inhibition of adipogenesis by Pref-1 has been well established in vitro as well as in vivo by ablation and overexpression of Pref-1. SRY (sex determining region Y)-box 9 (Sox9), a transcription factor expressed in preadipocytes to suppress CCAAT enhancer binding protein beta and (C/EBP) delta expression, is required to be down-regulated before adipocyte differentiation can proceed. By activating MAPK kinase/ERK, Pref-1 prevents down-regulation of Sox9, resulting in inhibition of adipogenesis. Furthermore, by inducing Sox9, Pref-1 promotes chondrogenic induction of mesenchymal cells but prevents chondrocyte maturation as well as osteoblast differentiation. Thus, Pref-1 directs multipotent mesenchymal cells toward the chondrogenic lineage but inhibits differentiation into adipocytes as well as osteoblasts and chondrocytes. Pref-1, encoded by an imprinted gene, has also been detected in progenitor cells in various tissues during regeneration and therefore may have a more general role in maintaining cells in an undifferentiated state.
Sul
Hei Sook
HS
Department of Nutritional Science and Toxicology, University of California, Berkeley, California 94720, USA. hsul@nature.berkeley.edu
D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000818:Animals; D002135:Calcium-Binding Proteins; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D017434:Protein Structure, Tertiary; D013234:Stem Cells / Q000166:cytology
D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C512925:Dlk1 protein, mouse; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D005947:Glucose