Characterization of Pref-1 and its inhibitory role in adipocyte differentiation.

Differentiation of preadipocytes to mature adipocytes is accompanied by marked increases in enzymes of lipid metabolism and cytoskeletal remodelling of fibroblastic preadipocytes to rounded lipid-filled mature adipocytes. Studies to date indicate this process is under the control of specific transcription factors, cell-cell and cell-environment interactions. Preadipocyte factor-1 (pref-1), a member of the EGF-like protein family, was identified during the differential screening of cDNAs expressed in differentiating preadipocytes. Multiple forms of the protein are present in 3T3-L1 preadipocytes with heterogeneity attributable both to alternate splicing and various post-translational modifications. Pref-1 is unique in that its expression is completely abolished during the maturation of preadipocytes to adipocytes. Moreover, blocking down-regulation via constitutive expression of pref-1 in preadipocytes inhibits their differentiation. The expression pattern of pref-1 in embryonic tissues and its presence in tumors indicate that in addition to its function in adipocyte differentiation, pref-1 may have a broader role in differentiation and development.