CHARACTERIZATION OF PREF-1 AND ITS INHIBITORY ROLE IN ADIPOCYTE DIFFERENTIATION

Differentiation of preadipocytes to mature adipocytes is accompanied b y marked increases in enzymes of lipid metabolism and cytoskeletal rem odelling 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 int eractions, Preadipocyte factor-1 (pref-1), a member of the EGF-like pr otein family, was identified during the differential screening of cDNA s expressed in differentiating preadipocytes. Multiple forms of the pr otein are present in 3T3-L1 preadipocytes with heterogeneity attribute d both to alternate splicing and various post-translational modificati ons, Pref-1 is unique in that its expression is completely abolished d uring the maturation of preadipocytes to adipocytes, Moreover, blockin g down-regulation via constitutive expression of pref-1 in preadipocyt es inhibits their differentiation. The expression pattern of pref-1 in embryonic tissues and its presence in tumors indicate that in additio n to its function in adipocyte differentiation, pref-1 may have a broa der role in differentiation and development.