Isoprenylation is Required for the Processing of the Lamin A Precursor

The nuclear lamina proteins, prelamin A, lamin B, and a 70-kD lamina-associated protein, are posttranslationally modified by a metabolite derived from mevalonate. This modification can be inhibited by treatment with (3-R,S)-3-fluoromevalonate, demonstrating that it is isoprenoid in nature. We have examined the association between isoprenoid metabolism and processing of the lamin A precursor in human and hamster cells. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by mevinolin (lovastatin) specifically depletes endogenous isoprenoid pools and inhibits the conversion of prelamin A to lamin A. Prelamin A processing is also blocked by mevalonate starvation of Mev-1, a CHO cell line auxotrophic for mevalonate. Moreover, inhibition of prelamin A processing by mevinolin treatment is rapidly reversed by the addition of exogenous mevalonate. Processing of prelamin A is, therefore, dependent on isoprenoid metabolism. Analysis of the conversion of prelamin A to lamin A by two independent methods, immunoprecipitation and two-dimensional nonequilibrium pH gel electrophoresis, demonstrates that a precursor-product relationship exists between prelamin A and lamin A. Analysis of R,S-[5-3H(N)]mevalonate-labeled cells shows that the rate of turnover of the isoprenoid group from prelamin A is comparable to the rate of conversion of prelamin A to lamin A. These results suggest that during the proteolytic maturation of prelamin A, the isoprenylated moiety is lost. A significant difference between prelamin A processing, and that of p21ras and the B-type lamins that undergo isoprenylation-dependent proteolytic maturation, is that the mature form of lamin A is no longer isoprenylated

The Academics Athletics Trade-off: Universities and Intercollegiate Athletics

This analysis focuses on several key issues in the Football Bowl Subdivision (FBS). The intrinsic benefits of athletic programs are discussed in the first section. Trends in graduation rates and academic performance among athletes and how they correlate with the general student body are discussed in the second section. Finally, an overview of the revenues and expenses of athletic department budgets are discussed in an effort to gain a better understanding of the allocation of funds to athletics. In spite of recent growth in revenues and expenses, the athletic department budget comprises on average only 5 percent of the entire university budget at an FBS school, though spending and revenues have increased dramatically in recent years. In the grand scheme of things, American higher education faces several other, arguably more pressing, areas of reform. However, athletics is a significant and growing dimension of higher education that warrants in-depth examination