Mutations affecting beta-tubulin folding and degradation.

Revertants of a colcemid-resistant Chinese hamster ovary cell line with an altered (D45Y) beta-tubulin have allowed the identification of four cis-acting mutations (L187R, Y398C, a 12-amino acid in-frame deletion, and a C-terminal truncation) that act by destabilizing the mutant tubulin and preventing it from incorporating into microtubules. These unstable beta-tubulins fail to form heterodimers and are predominantly found in association with the chaperonin CCT, suggesting that they cannot undergo productive folding. In agreement with these in vivo observations, we show that the defective beta-tubulins do not stably interact with cofactors involved in the tubulin folding pathway and, hence, fail to exchange with beta-tubulin in purified alphabeta heterodimers. Treatment of cells with MG132 causes an accumulation of the aberrant tubulins, indicating that improperly folded beta-tubulin is degraded by the proteasome. Rapid degradation of the mutant tubulin does not elicit compensatory changes in wild-type tubulin synthesis or assembly. Instead, loss of beta-tubulin from the mutant allele causes a 30-40% decrease in cellular tubulin content with no obvious effect on cell growth or survival.

A Tale of Two States: What We Learn from California and Texas

Teen birth rates and teen pregnancy prevention strategies vary widely across individual states in the US, which has the highest overall teen birth rate among developed nations. California and Texas, the two most populous states currently accounting for a quarter of all teen births, have taken very different approaches to addressing adolescent reproductive health. This case study examines the racial/ethnic composition and socioeconomic factors of these two states from 1981 to 2008. State programs and policies implemented between 1991 and 2008 as well as changes in access to contraception and public–private partnerships are discussed. Based on the lessons learned from California, a similar multifaceted campaign in Texas may be effective in reducing teen births.