Search results for "Post-translational regulation"
showing 6 items of 6 documents
Mcl-1 targeting could be an intriguing perspective to cure cancer
2018
The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis. Cancer chemotherapy determines various kinds of responses, such as senescence and autophagy; however, the ideal response to chemotherapy…
Intestinal epithelial HuR modulates distinct pathways of proliferation and apoptosis and attenuates small intestinal and colonic tumor development.
2014
Abstract HuR is a ubiquitous nucleocytoplasmic RNA-binding protein that exerts pleiotropic effects on cell growth and tumorigenesis. In this study, we explored the impact of conditional, tissue-specific genetic deletion of HuR on intestinal growth and tumorigenesis in mice. Mice lacking intestinal expression of HuR (Hur IKO mice) displayed reduced levels of cell proliferation in the small intestine and increased sensitivity to doxorubicin-induced acute intestinal injury, as evidenced by decreased villus height and a compensatory shift in proliferating cells. In the context of Apcmin/+ mice, a transgenic model of intestinal tumorigenesis, intestinal deletion of the HuR gene caused a three-fo…
Post-Translational Regulation of CYP450s Metabolism As Revealed by All-Atoms Simulations of the Aromatase Enzyme.
2019
Phosphorylation by kinases enzymes is a widespread regulatory mechanism able of rapidly altering the function of target proteins. Among these are cytochrome P450s (CYP450), a superfamily of enzymes performing the oxidation of endogenous and exogenous substrates thanks to the electron supply of a redox partner. In spite of its pivotal role, the molecular mechanism by which phosphorylation modulates CYP450s metabolism remains elusive. Here by performing microsecond-long all-atom molecular dynamics simulations, we disclose how phosphorylation regulates estrogen biosynthesis, catalyzed by the Human Aromatase (HA) enzyme. Namely, we unprecedentedly propose that HA phosphorylation at Y361 markedl…
NO-Based Signaling in Plants
2006
In animals, nitric oxide (NO) is an endogenously produced radical involved in cell communication and signal transduction. Its functions in plants are currently being discovered at an unprecedented pace, and insight into NO-derived mechanisms has mainly been gained from research on signal transduction. Numerous studies have firmly placed NO as one component of the signal perception–transduction network that connects plant responses to primary signals, including hormones, elicitors of defence responses or abiotic stresses. Protein kinases and the second messengers Ca 2+, cGMP, and cADPR convey part of the NO signal within cells. Furthermore, NO-based protein modifications are emerging as broa…
Functional regulation of HIF-1α under normoxia--is there more than post-translational regulation?
2011
The hypoxia-inducible factor-1 (HIF-1) is an oxygen-regulated transcriptional activator playing a pivotal role in mammalian physiology and disease pathogenesis, e.g., HIF-1 is indispensable in a broad range of developmental stages in different tumors. Its post-translational regulation via PHDs under the influence of hypoxia is widely investigated and accepted. Different non-hypoxic stimuli such as lipopolysaccharides (LPS), thrombin, and angiotensin II (Ang II), have been proven to enhance HIF-1 levels through activation of regulative mechanisms distinct from protein stabilization. Some of these stimuli specifically regulate HIF-1α at the transcriptional, post-transcriptional, or translatio…