Abstract:
BACKGROUND:The modest efficacy of available therapies for Hepatocellular carcinoma (HCC) indicates the need to develop novel therapeutic approaches. For the proteasome inhibitor Bortezomib (BZB), potentially attractive for HCC treatment, the mechanism of action is largely unknown. The BZB effect on E2Fs and the E2Fs control on the peptidylproline cis-trans isomerase (Pin1), prompted us to explore the BZB effect on the Pin1-E2F1 axis. METHODS:The tumorigenic cell line HuH7 together with the non-tumorigenic cells IHH and the human pluripotent stem cell derived hepatocytes (hPSC-H), were used as cellular models of HCC and normal liver cells, respectively. RESULTS:BZB reduces HuH7 growth as shown by cell counting, cell vitality test and cell cycle analysis; this is paralleled by the decrease of Pin1, E2F1, cyclin A2 and of the hyper-phosphorylated pRB. Pin1-E2F1 axis impairment justifies the anti-proliferative effect since Pin-E2F1 depletion decreases HuH7 growth while the over-expression rescues BZB-induced inhibition of proliferation. Moreover, Pin1-E2F1 promote HuH7 growth via the up-regulation of cyclin D1, cyclin E, cyclin A2, E2F2 and in part E2F3. Finally, in the control cells IHH and hPSC-H, BZB effect on cell vitality is not irrelevant, a fact correlated to the cellular proliferation rate. Thus, BZB effect on healthy liver tissue may not be entirely negligible hence caution should be exercised in its use in liver regeneration processes. CONCLUSION:For the first time we prove the functional involvement of the Pin1-E2F1 axis in the anti-proliferative effect of BZB indicating Pin1-E2F as an attractive target to control HCC cell growth.
journal_name
Biochimiejournal_title
Biochimieauthors
Farra R,Dapas B,Baiz D,Tonon F,Chiaretti S,Del Sal G,Rustighi A,Elvassore N,Pozzato G,Grassi M,Grassi Gdoi
10.1016/j.biochi.2015.02.015subject
Has Abstractpub_date
2015-05-01 00:00:00pages
85-95eissn
0300-9084issn
1638-6183pii
S0300-9084(15)00050-4journal_volume
112pub_type
杂志文章相关文献
BIOCHIMIE文献大全abstract::Using a rapid FPLC procedure for the separation of calpain I, calpain II and the inhibitor calpastatin from pork meat, results of proteolytic and inhibitory activity were obtained. Duplicate measurements showed variation coefficients less than 0.13. Compared to others we found lower calpain I activity 1 h post-mortem....
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/0300-9084(93)90041-p
更新日期:1993-01-01 00:00:00
abstract::Epidemiological studies have demonstrated that the diabetes mellitus is a serious health burden for both governments and healthcare providers. The present study was hypothesized to evaluate the antihyperglycemic potential of fraxetin by determining the activities of key enzymes of carbohydrate metabolism in streptozot...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2013.06.013
更新日期:2013-10-01 00:00:00
abstract::The ability to measure the thermodynamic stability of proteins with precision is important for both academic and applied research. Such measurements rely on mathematical models of the protein denaturation profile, i.e. the relation between a global protein signal, corresponding to the folding states in equilibrium, an...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2015.11.013
更新日期:2016-02-01 00:00:00
abstract::The binding of Ca2+ to membrane models composed of diplamitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine (DPPE) 15N-labeled in the polar head group was investigated at pH 8.5 and pH 9.4 by 15N-NMR spectroscopy. Both phospholipids exhibit a decrease in the chemical shift anisotropy, indicating c...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/0300-9084(89)90143-0
更新日期:1989-01-01 00:00:00
abstract::NikR proteins are bacterial metallo-regulatory transcription factors that control the expression of the nickel uptake system and/or nickel containing enzymes such as urease, and are involved in the acid stress response. Here, a comparative study is reported on NikR from Helicobacter pylori (HpNikR) and Escherichia col...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2006.07.016
更新日期:2006-11-01 00:00:00
abstract::The quest for effective anticancer therapeutics continues to be extensively pursued. Over the past century, several drugs have been developed, however, a majority of these drugs have a poor therapeutic index and increased toxicity profile. Hence, there still exists ample opportunity to discover safe and effective anti...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2020.12.024
更新日期:2021-01-06 00:00:00
abstract::Intracellular cytoplasmic peptidoglycan (PG) intermediate levels were determined in Staphylococcus aureus during log-phase growth in enriched media. Levels of UDP-linked intermediates were quantitatively determined using ion pairing LC-MS/MS in negative mode, and amine intermediates were quantitatively determined ster...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2015.11.017
更新日期:2016-02-01 00:00:00
abstract::The field of immunometabolism has come a long way in the past decade, leading to the emergence of a new role for white adipose tissue (WAT) that is now recognized to stand at the junction of immune and metabolic regulations. Interestingly, a crucial role of the abundant and heterogeneous immune population present in W...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2015.06.012
更新日期:2016-05-01 00:00:00
abstract::So far, no efficient affinity chromatography for CCK receptor purification has been reported that prevented obtention of sequenceable amounts of purified receptor. In this work, 10% of plasma membrane receptor sites were specifically cross-linked with the photoreactive cleavable agonist 125I-ASD-[Thr28, Ahx31]-CCK-25-...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/0300-9084(92)90039-h
更新日期:1992-02-01 00:00:00
abstract::Adipose tissue is an endocrine organ that plays an essential role in regulating several metabolic functions through the secretion of biological mediators called "adipokines". Dysregulation of adipokines plays a crucial role in obesity-related diseases. Adiponectin (APN) is the most abundant adipokine accounting for th...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2012.06.030
更新日期:2012-10-01 00:00:00
abstract::Aptamers are short single-stranded nucleic acid molecules that are selected in vitro from a large random sequence library based on their high and specific affinity to a target molecule by a process known as SELEX. Cell-SELEX that employs whole living cells overexpressing the defined cell surface proteins (for selectio...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2016.09.018
更新日期:2016-12-01 00:00:00
abstract::The kinetic and regulatory properties of purified pigeon heart muscle AMP deaminase were investigated. In the presence of 100 mM potassium chloride, the enzyme exhibited a slightly sigmoidal type of kinetics. Addition of ATP to the incubation medium changed the reaction rate versus substrate concentration plot into a ...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/0300-9084(87)90243-4
更新日期:1987-02-01 00:00:00
abstract::Labeling of 21-kDa material was observed when bovine brain soluble fraction was incubated with [adenylate-32P]NAD+ in the presence of GTP. The 21-kDa substrate, slightly smaller than C3 substrate in size, was labeled even without C3 exoenzyme. GTP could be replaced by nucleoside triphosphates other than ATP while ATP ...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/s0300-9084(97)86150-0
更新日期:1997-07-01 00:00:00
abstract::A series of halomethylated derivatives of dihydrocoumarins has been found to inhibit irreversibly proteases and esterases. alpha-Chymotrypsin, subtilish, elastase are rapidly inactivated in the presence of these compounds, while trypsin, kallicrein, papain are inhibited more slowly. Esterases like acetylcholinesterase...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/s0300-9084(77)80140-5
更新日期:1977-01-01 00:00:00
abstract::The quantitative formalism called Metabolic Control Theory makes it possible to be precise in discussions of metabolic control. To illustrate this, I will mention 2 experimental systems where free energy is converted from one form to another, i.e., bacteriorhodopsin liposomes and mitochondrial oxidative phosphorylatio...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/0300-9084(89)90071-0
更新日期:1989-08-01 00:00:00
abstract::Information on the subcellular localization of bacterial proteins is essential for protein function prediction, genome annotation and drug design. Here we proposed a novel approach to predict the subcellular localization of bacterial proteins by fusing features from position-specific score matrix (PSSM), Gene Ontology...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2014.06.001
更新日期:2014-09-01 00:00:00
abstract::Cysteine-rich secretory proteins (CRISPs), characterized by 16 conserved cysteines, are distributed in a wide range of organisms, such as secernenteas, amphibians, reptiles and mammals. In the previous studies, a novel CRISP family member (cysteine-rich buccal gland protein, CRBGP) was separated from the buccal gland ...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2015.11.020
更新日期:2016-04-01 00:00:00
abstract::Bacteria of the Lactococcus (formerly lactic Streptococcus) genus are described to emphasize certain less well-known facts of importance in their successful use as dairy starters. Other streptococci (non-rod forms) are briefly characterized to emphasize their usefulness in industrial milk fermentations. ...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/0300-9084(88)90087-9
更新日期:1988-04-01 00:00:00
abstract::Anaerobiospirillum succiniciproducens phosphoenolpyruvate (PEP) carboxykinase catalyses the reversible metal-dependent formation of oxaloacetate (OAA) and ATP from PEP, ADP and CO(2). Mutations of PEP carboxykinase have been constructed where the residues His(225) and Asp(263), two residues of the enzyme's putative Mn...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2003.10.013
更新日期:2004-01-01 00:00:00
abstract::Maximum 125I-IGF-I/Sm-C total binding to chick embryo fibroblasts was 3% at +37 degrees C and decreased to less than 1% in presence of 2.8 X 10(-9) M unlabelled IGF-I/Sm-C. Insulin did not compete with IGF-I/Sm-C for the binding to cells. Biological action of IGF-I/Sm-C was evaluated on 2-deoxyglucose and alpha-aminoi...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/s0300-9084(85)80118-8
更新日期:1985-10-01 00:00:00
abstract::The mechanism responsible for creating the division site in the right place at the right time in bacteria is unknown. It has been attributed to the formation of proteolipid domains in the cytoplasmic membrane surrounding the nucleoids. We interpret the growing evidence for this hypothesis by invoking hyperstructures, ...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/s0300-9084(00)01203-7
更新日期:2001-01-01 00:00:00
abstract::Protein-induced DNA bridging and looping is a common mechanism for various and essential processes in bacterial chromosomes. This mechanism is preserved despite the very different bacterial conditions and their expected influence on the thermodynamic and kinetic characteristics of the bridge formation and stability. O...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2017.08.002
更新日期:2017-11-01 00:00:00
abstract::The polysaccharide mixture obtained by hot water extraction of Aloe vahombe leaves is composed of at least four different paritally acetylated glucomannans which differ in molecular weight, glucose to mannose ratios and acetyl contents. Furthermore, one fraction contains a small but significant amount of protein which...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/s0300-9084(86)80187-0
更新日期:1986-09-01 00:00:00
abstract::OURCIN is a tool to build expert systems, which was developed by a joint team from INRIA and SEMA. We emphasized developing on this system the ergonomic features which make Expert Systems a comfortable and interesting approach for knowledge engineering. ...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/s0300-9084(85)80267-4
更新日期:1985-05-01 00:00:00
abstract::Mitochondria are essential organelles and consequently proper expression and maintenance of the mitochondrial genome are indispensable for proper cell function. The mitochondrial Suv3 (SUPV3L1) helicase is known to have a central role in mitochondrial RNA metabolism and to be essential for maintenance of mitochondrial...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/j.biochi.2014.11.003
更新日期:2015-01-01 00:00:00
abstract::Alteration of the epigenome is associated with a wide range of human diseases. Therefore, deciphering the pathways that regulate the epigenetic modulation of gene expression is a major milestone for the understanding of diverse biological mechanisms and subsequently human pathologies. Although often evoked, little is ...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2007.07.022
更新日期:2008-01-01 00:00:00
abstract::Rhodospirillum salexigens is a moderately halophilic purple phototrophic bacterium which grows optimally in 8% NaCl. The amino acid sequences of the two principal soluble cytochromes c have been determined. One of these is a cytochrome c2, similar in size to mitochondrial cytochrome c. While clearly of the same sequen...
journal_title:Biochimie
pub_type: 杂志文章
doi:10.1016/0300-9084(94)90135-x
更新日期:1994-01-01 00:00:00
abstract::The fatty acid composition of animal products (eggs, milk and meat) is the reflect of both the tissue fatty acid biosynthesis and the fatty acid composition of ingested lipids. This relationship is stronger in monogastrics (pigs, poultry and rabbits) than in ruminants, where dietary fatty acids are hydrogenated in the...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2010.02.027
更新日期:2011-01-01 00:00:00
abstract::A major incentive in inhibitor research is that control of limited proteolysis constitutes a valuable pharmacological tool. Protease inhibitors have proved to be successful in influencing pathogenesis in many experimental models but a breakthrough to use in human therapy has mainly been restricted to aprotinin and ang...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/0300-9084(91)90084-e
更新日期:1991-01-01 00:00:00
abstract::Epithelial Ca(2+)-regulation, which governs cornified envelope formation in the skin epidermis and hair follicles, closely coincides with the expression of S100A3, filaggrin and trichohyalin, and the post-translational modification of these proteins by Ca(2+)-dependent peptidylarginine deiminases. This review summariz...
journal_title:Biochimie
pub_type: 杂志文章,评审
doi:10.1016/j.biochi.2011.05.028
更新日期:2011-12-01 00:00:00