On Overreaching, or Why Rick Perry May Save the Voting Rights Act but Destroy Affirmative Action

Abstract The State of Texas is presently staking out two positions that are not typically pursued by a single litigant. On the one hand, Texas is seeking the invalidation of the Voting Rights Act, and, on the other, the State is now defending the validity of the expansive race-based affirmative action policy it uses at its flagship university. This Essay presses the claim that Texas has increased the chance it will lose in both Texas v. Holder and Fisher v. University of Texas because it has opted to stake out markedly extreme positions in each. I argue that Texas would be more likely to succeed had it chosen to temper both its actions and claims in the pending cases. As it stands, Texas's assertive stance in Fisher promises to bolster the aversion many Justices already feel towards affirmative action. With regard to the VRA, however, Texas's uncompromising approach to the regime may prove to be the VRA's best defense. As recent redistricting and voter ID decisions suggest, Texas's stance may be provide what is arguably better evidence for why the statute remains necessary than anything proffered by the VRA's many supporters. Indeed, the State's aggressively hostile stance towards the VRA has the potential to destabilize judicial misgivings about the statute, and, if not fully reverse them, postpone their implementation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98443/1/elj%2E2012%2E1147.pd

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization