TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells.

SOLUTION: Which is the receptor for substrates of Chaperone Mediated Autophagy?

PROBLEM: Hoping to rebound from their three-game losing streak, the Raiders flew to Dolphin Stadium for a Week 11 duel with the Miami Dolphins. In the first quarter, Oakland trailed early as Dolphins WR Ted Ginn, Jr. got a 40-yard TD run. In the second quarter, the Raiders responded with kicker Sebastian Janikowski getting a 21-yard field goal. In the third quarter, Oakland started to catch up as DE Jay Richardson sacked QB Chad Pennington in his own endzone for a safety. Miami would answer with RB Patrick Cobbs getting a 10-yard TD run. In the fourth quarter, the Raiders took the lead as Janikowski got a 37-yard field goal, along with WR Johnnie Lee Higgins returning a punt 93 yards for a touchdown. However, the Dolphins sealed Oakland's fate as kicker Dan Carpenter nailed a 38-yard field goal.

SOLUTION: Which player scored a safety?

PROBLEM: Desmosomes are cell-cell adhesion structures that integrate cytoskeletal networks. In addition to binding intermediate filaments, the desmosomal protein desmoplakin (DP) regulates microtubule reorganization in the epidermis. In this paper, we identify a specific subset of centrosomal proteins that are recruited to the cell cortex by DP upon epidermal differentiation. These include Lis1 and Ndel1, which are centrosomal proteins that regulate microtubule organization and anchoring in other cell types. This recruitment was mediated by a region of DP specific to a single isoform, DPI. Furthermore, we demonstrate that the epidermal-specific loss of Lis1 results in dramatic defects in microtubule reorganization. Lis1 ablation also causes desmosomal defects, characterized by decreased levels of desmosomal components, decreased attachment of keratin filaments, and increased turnover of desmosomal proteins at the cell cortex. This contributes to loss of epidermal barrier activity, resulting in completely penetrant perinatal lethality. This work reveals essential desmosome-associated components that control cortical microtubule organization and unexpected roles for centrosomal proteins in epidermal function.

SOLUTION:
What are the structures formed when keratin molecules come together?