An Inhibitory Role of the G-Protein Regulator AGS3 in mTOR-Dependent Macroautophagy

Macroautophagy is a cellular process whereby the cell sequesters and recycles cytosolic constituents in a lysosome-dependent manner. It has also been implicated in a number of disorders, including cancer and neurodegeneration. Although a previous report that AGS3 over-expression promotes macroautophagy suggests a stimulatory role of AGS3 in this process, we have found that knock-down of AGS3, unexpectedly, also induces macroautophagy, indicating an inhibitory function of endogenous AGS3 in macroautophagy. Interestingly, AGS3 phosphorylation is decreased upon induction of mammalian target of rapamycin (mTOR)-dependent macroautophagy. Moreover, unlike wild-type AGS3, over-expression of an AGS3 mutant lacking this modification fails to enhance macroautophagic activity. These observations imply that AGS3 phosphorylation may participate in the modulation of macroautophagy

Health care quality from the patients' perspective: a comparative study between an old and a new, high-tech hospital

publishedVersio

Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1

Beclin 1, a subunit of the class III phosphatidylinositol 3-kinase complex, is a tumour suppressor with a central role in endocytic trafficking, cytokinesis and the cross-regulation between autophagy and apoptosis. Interestingly, not only reduced expression but also overexpression of Beclin 1 is correlated with cancer development and metastasis. Thus it seems necessary for the cell to balance the protein levels of Beclin 1. In the present study we describe a regulatory link between Beclin 1 and the ubiquitin ligase Nedd4 (neural-precursor-cell-expressed developmentally down-regulated 4). We establish Nedd4 as a novel binding partner of Beclin 1 and demonstrate that Nedd4 polyubiquitinates Beclin 1 with Lys11- and Lys63-linked chains. Importantly, Nedd4 expression controls the stability of Beclin 1, and depletion of the Beclin 1-interacting protein VPS34 causes Nedd4-mediated proteasomal degradation of Beclin 1 via Lys11-linked polyubiquitin chains. Beclin 1 is thus the first tumour suppressor reported to be controlled by Lys11-linked polyubiquitination

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd

Improvement of the quality of low-fat cheese using a two step strategy

acceptedVersio

Do all cloned animals age in the same way - telomeres and telomerase, is there any difference?

In discussions regarding modern biotechnology, cloning is the word commonly associated with this field of knowledge. This is a direct result of the world famous cloning of "Dolly" in 1997. Even though, the technology have been developed several years ago it is still in its infancy, and years might go by before good solutions are developed. What has to be noticed is that only a small percentage of cloning experiments will lead to viable offspring, and in addition, the lifespan of cloned animals seems to be shorter than their donor ancestors and sibling from normal reproduction. "Dolly's" early death led to many questions, among them; did the cloning process accelerate aging? Subsequently, many studies have been performed to find a reason for Dolly early aging. As a result, it was stated that this animal inherited shortened telomeres from the donor cell, and that was the reason for the rapid aging process. Since then many various animals have been successfully cloned. Different observations suggest that the age of the donor cell used in somatic cell nuclear transfer technique not necessarily affect the aging of cloned animals. The telomere length in animals that underwent the cloning procedure vary based on species, age, gender, cell type, culturing environment and so on. It is also important to consider genetic facts in donor animals, when telomere length seems to vary within the species. It is shown that telomere length can give an indication on cell senescence, but is not necessarily related to the aging of the organism. Different results presented in the articles imply that there is no straightforward answer when comes to early aging of cloned animals. Still there are many unanswered questions. Future research will provide us with deeper knowledge of these mechanisms, necessary for optimizing of the cloning procedure

Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain.

In the present study, we investigate the mechanism for the protein kinase A (PKA)-mediated activation of C-terminal Src kinase (Csk). Although isolated Csk kinase domain was phosphorylated at Ser(364) by PKA to the same stoichiometry as wild-type Csk, significant activation of the isolated Csk kinase domain by PKA was observed only in the presence of the purified Src homology 3 domain (SH3 domain). Furthermore, the interaction between the SH3 and kinase domains was facilitated by PKA-mediated phosphorylation of the kinase domain, as evaluated by surface plasmon resonance. This suggests that an overall structural domain organization and interaction between the kinase and SH3 domains are important for the activity of Csk and its regulation by PKA