No abstract

Regulatory functions of the ubiquitin-proteasome system (UPS) are exercised mainly by the ubiquitin ligases and deubiquitinating enzymes. Degradation of apoptotic proteins by UPS is central to the maintenance of cell health, and deregulation of this process is associated with several diseases including tumors, neurodegenerative disorders, diabetes, and inflammation. Therefore, it is the view that interrogating protein turnover in cells can offer a strategy for delineating disease-causing mechanistic perturbations and facilitate identification of drug targets. In this review, we are summarizing an overview to elucidate the updated knowledge on the molecular interplay between the apoptosis and UPS pathways. We have condensed around 100 enzymes of UPS machinery from the literature that ubiquitinates or deubiquitinates the apoptotic proteins and regulates the cell fate. We have also provided a detailed insight into how the UPS proteins are able to fine-tune the intrinsic, extrinsic, and p53-mediated apoptotic pathways to regulate cell survival or cell death. This review provides a comprehensive overview of the potential of UPS players as a drug target for cancer and other human disorders.

No abstract

Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.

We assessed the suitability of 9 internal control genes (ICG) in milk somatic cells of lactating cows to find suitable reference genes for use in quantitative PCR (qPCR). Eighteen multiparous lactating Sahiwal cows were used, 6 in each of 3 lactation stages: early (25 ± 5 d in milk), mid (160 ± 15 d in milk), and late (275 ± 25 d in milk) lactation. Nine candidate reference genes [glyceraldehyde 3-phosphate dehydrogenase (GAPDH), protein phosphatase 1 regulatory subunit 11 (PPP1R11), β-actin (ACTB), β-2 microglobulin (B2M), 40S ribosomal protein S15a (RPS15A), ubiquitously expressed transcript (UXT), mitochondrial GTPase 1 (MTG1), 18S rRNA (RN18S1), and ubiquitin (UBC)] were evaluated. Three genes, β-casein (CSN2), lactoferrin (LTF), and cathelicidin (CAMP) were chosen as target genes. Very high amplification was observed in 7 ICG and very low level amplification was observed in 2 ICG (UXT and MTG1). Thus, UXT and MTG1 were excluded from further analysis. The qPCR data were analyzed by 2 software packages, geNorm and NormFinder, to determine suitable reference genes, based on their stability and expression. Overall, PPP1R11, ACTB, UBC, and GAPDH were stably expressed among all candidate reference genes. Therefore, these genes could be used as ICG for normalization of qPCR data in milk somatic cells through lactation.

The contents of copper, zinc and protein were determined in cortex and nucleus sections of cortical and nuclear cataracts. The results show that copper and zinc content increased in both types of cataracts, although more in the cortex than nucleus sections of the cataractous lenses.

No abstract

The ubiquitin proteasome system (UPS) plays an imperative role in many critical cellular processes, frequently by mediating the selective degradation of misfolded and damaged proteins and also by playing a non-degradative role especially important as in many signaling pathways. Over the last three decades, accumulated evidence indicated that UPS proteins are primal modulators of cell cycle progression, DNA replication, and repair, transcription, immune responses, and apoptosis. Comparatively, latest studies have demonstrated a substantial complexity by the UPS regulation in the heart. In addition, various UPS proteins especially ubiquitin ligases and proteasome have been identified to play a significant role in the cardiac development and dynamic physiology of cardiac pathologies such as ischemia/reperfusion injury, hypertrophy, and heart failure. However, our understanding of the contribution of UPS dysfunction in the plausible development of cardiac pathophysiology and the complete list of UPS proteins regulating these afflictions is still in infancy. The recent emergence of the roles of TNF receptor-associated factor (TRAFs) and deubiquitinating enzymes (DUBs) superfamily in hypertrophic cardiomyopathy has enhanced our knowledge. In this review, we have mainly compiled the TRAF superfamily of E3 ligases and few DUBs proteins with other well-documented E3 ligases such as MDM2, MuRF-1, Atrogin-I, and TRIM 32 that are specific to myocardial hypertrophy. In this review, we also aim to highlight their expression profile following physiological and pathological stimulation leading to the onset of hypertrophic phenotype in the heart that can serve as biomarkers and the opportunity for the development of novel therapies.