The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasomemediated degradation of PPAR gamma

Peroxisome proliferator-activated receptor gamma (PPAR??) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPAR?? is regulated not only by ligands but also by post-translational modifications (PTMs). In this study, we demonstrate that a novel E3 ligase of PPAR??, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPAR??, leading to its proteasome-dependent degradation. During adipocyte differentiation, both TRIM25 mRNA and protein expression significantly decreased and negatively correlated with the expression of PPAR??. The stable expression of TRIM25 reduced PPAR?? protein levels and suppressed adipocyte differentiation in 3T3-L1 cells. In contrast, the specific knockdown of TRIM25 increased PPAR?? protein levels and stimulated adipocyte differentiation. Furthermore, TRIM25-knockout mouse embryonic fibroblasts (MEFs) exhibited an increased adipocyte differentiation capability compared with wild-type MEFs. Taken together, these data indicate that TRIM25 is a novel E3 ubiquitin ligase of PPAR?? and that TRIM25 is a novel target for PPAR??-associated metabolic diseases

SS18 Together with Animal-Specific Factors Defines Human BAF-Type SWI/SNF Complexes

Contains fulltext : 94049.pdf (publisher's version ) (Open Access

Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy

Estrogen receptor (ER) has a crucial role in normal breast development and is expressed in the most common breast cancer subtypes. Importantly, its expression is very highly predictive for response to endocrine therapy. Current endocrine therapies for ER-positive breast cancers target ER function at multiple levels. These include targeting the level of estrogen, blocking estrogen action at the ER, and decreasing ER levels. However, the ultimate effectiveness of therapy is limited by either intrinsic or acquired resistance. Identifying the factors and pathways responsible for sensitivity and resistance remains a challenge in improving the treatment of breast cancer. With a better understanding of coordinated action of ER, its coregulatory factors, and the influence of other intracellular signaling cascades, improvements in breast cancer therapy are emerging

Authoritarianism and Attitudes toward Contemporary Social Issues

Three studies were conducted to examine the relevance of authoritarianism to contemporary social attitudes, with special emphasis on AIDS, drug use, and the environment. In Studies 1 and 2, students scoring higher on authoritarianism (measured by Byrne's balanced F scale and Altemeyer's Right-Wing Authoritarianism Scale, respectively) were more likely to endorse harsh, punitive sentiments and solutions to the problems of AIDS and drugs and less likely to endorse more egalitarian ones. These two issues are presumed to represent a threat to the "American way of life" and provide clear out-groups for authoritarian aggression. Regarding the environment, authoritarians express hostility toward the environmental movement, rather than toward polluters. In Study 3, authoritarianism was further related to attitudes on abortion, child abuse, homelessness, the space program, the trade deficit, political changes in the Soviet Union, and the purposes of colleges and universities. These results show that the concept of authoritarianism is applicable to attitudes on many important issues of the 1 990s.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68780/2/10.1177_0146167293192006.pd