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Source: The Biochemical Journal

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Total 51 results found since Jan 2013.

Characterization of uridine-cytidine kinase like-1 nucleoside kinase activity and its role in tumor growth
Biochem J. 2022 May 18:BCJ20210770. doi: 10.1042/BCJ20210770. Online ahead of print.ABSTRACTUridine-cytidine kinase like-1 (UCKL-1) is a largely uncharacterized protein with high sequence similarity to other uridine-cytidine kinases (UCKs). UCKs play an important role in the pyrimidine salvage pathway, catalyzing the phosphorylation of uridine and cytidine to UMP and CMP, respectively. Only two human UCKs have been identified, UCK1 and UCK2. Previous studies have shown both enzymes phosphorylate uridine and cytidine using ATP as the phosphate donor. No studies have evaluated the kinase potential of UCKL-1. We cloned and pu...
Source: The Biochemical Journal - May 18, 2022 Category: Biochemistry Authors: Emily Matchett Elise C Ambrose Jacki Kornbluth Source Type: research

IKK α plays a major role in canonical NF-kB signalling in colorectal cells
Biochem J. 2022 Jan 14:BCJ20210783. doi: 10.1042/BCJ20210783. Online ahead of print.ABSTRACTInhibitor of kappa B (IκB) kinase β (IKKβ) has long been viewed as the dominant IKK in the canonical nuclear factor-κB (NF-κB) signalling pathway, with IKKα being more important in non-canonical NF-κB activation. Here we have investigated the role of IKKα and IKKβ in canonical NF-κB activation in colorectal cells using CRISPR-Cas9 knock-out cell lines, siRNA and selective IKKβ inhibitors. IKKα and IKKβ were redundant for IκBα phosphorylation and turnover since loss of IKKα or IKKβ alone had little (SW620 cells) or n...
Source: The Biochemical Journal - January 14, 2022 Category: Biochemistry Authors: Jack A Prescott Kathryn Balmanno Jennifer P Mitchell Hanneke Okkenhaug Simon J Cook Source Type: research

Investigation of USP30 inhibition to enhance Parkin-mediated mitophagy: tools and approaches
Biochem J. 2021 Oct 27:BCJ20210508. doi: 10.1042/BCJ20210508. Online ahead of print.ABSTRACTMitochondrial dysfunction is implicated in Parkinson disease (PD). Mutations in Parkin, an E3 ubiquitin ligase, can cause juvenile-onset Parkinsonism probably through impairment of mitophagy. Inhibition of the de-ubiquitinating enzyme USP30 may counter this effect to enhance mitophagy. Using different tools and cellular approaches, we wanted to independently confirm this claimed role for USP30. Pharmacological characterization of additional tool compounds that selectively inhibit USP30 are reported. The consequence of USP30 inhibiti...
Source: The Biochemical Journal - October 27, 2021 Category: Biochemistry Authors: Eliona Tsefou Alison S Walker Emily H Clark Amy Rose Hicks Christin Luft Kunitoshi Takeda Toru Watanabe Bianca Ramazio James M Staddon Thomas Briston Robin Ketteler Source Type: research

BACH1, the master regulator of oxidative stress, has a dual effect on CFTR expression
Biochem J. 2021 Oct 4:BCJ20210252. doi: 10.1042/BCJ20210252. Online ahead of print.ABSTRACTThe cystic fibrosis transmembrane conductance regulator (CFTR) gene lies within a TAD in which multiple cis-regulatory elements (CREs) and transcription factors (TFs) regulate its cell-specific expression. The CREs are recruited to the gene promoter by a looping mechanism that depends upon both architectural proteins and specific TFs. An siRNA screen to identify TFs coordinating CFTR expression in airway epithelial cells suggested an activating role for BTB Domain and CNC Homolog 1 (BACH1). BACH1 is a ubiquitous master regulator of t...
Source: The Biochemical Journal - October 4, 2021 Category: Biochemistry Authors: Monali NandyMazumdar Alekh Paranjapye James Browne Shiyi Yin Shih-Hsing Leir Ann Harris Source Type: research

Integrin αVβ1 Regulates Procollagen I Production through a Non-canonical Transforming Growth Factor β Signaling Pathway in Human Hepatic Stellate Cells
Biochem J. 2021 Apr 20:BCJ20200749. doi: 10.1042/BCJ20200749. Online ahead of print.ABSTRACTHepatic stellate cells (HSCs) are thought to play key roles in the development of liver fibrosis. Extensive evidence has established the concept that αV integrins are involved in the activation of latent transforming growth factor β (TGF-β), a master regulator of the fibrotic signaling cascade. Based on mRNA and protein expression profiling data, we found that αVβ1 integrin is the most abundant member of the αV integrin family in either quiescent or TGF-β1-activated primary human HSCs. Unexpectedly, either a selective αVβ1 ...
Source: The Biochemical Journal - April 20, 2021 Category: Biochemistry Authors: Zuoning Han Yanling Ma Gary Cao Zhengping Ma Ruihua Chen Mary Ellen Cvijic Dong Cheng Source Type: research

A role for PAK1 mediated phosphorylation of β-catenin Ser552 in the regulation of insulin secretion.
Abstract The presence of adherens junctions and the associated protein β-catenin are requirements for the development of glucose stimulated insulin secretion (GSIS) in β-cells. Evidence indicates that modulation of β-catenin function in response to changes in glucose levels can modulate the levels of insulin secretion from β-cells but the role of β-catenin phosphorylation in this process has not been established. We find that a Ser552Ala version of β-catenin attenuates glucose stimulated insulin secretion indicating a functional role for Ser552 phosphorylation of β-catenin in insulin secretion. This is ass...
Source: The Biochemical Journal - February 19, 2021 Category: Biochemistry Authors: Sorrenson B, Dissanayake WC, Hu F, Lee KL, Shepherd PR Tags: Biochem J Source Type: research

MAPK-interacting kinase 2 (MNK2) regulates adipocyte metabolism independently of its catalytic activity.
Abstract The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are serine/threonine protein kinases that are activated by the ERK1/2 (extracellular-regulated kinase) and p38α/β MAPK pathways. The MNKs have previously been implicated in metabolic disease and shown to mediate diet-induced obesity. In particular, knockout of MNK2 in mice protects from the weight gain induced by a high-fat diet. These and other data suggest that MNK2 regulates expansion of adipose tissue, a stable, long-term energy reserve that plays an important role in regulating whole-body energy homeostasis. Using the well-estab...
Source: The Biochemical Journal - July 9, 2020 Category: Biochemistry Authors: Merrett J, Xie J, Psaltis PJ, Proud CG Tags: Biochem J Source Type: research

Cr(VI)-induced  overactive mitophagy contributes to mitochondrial loss and cytotoxicity in L02 hepatocytes.
Cr(VI)-induced overactive mitophagy contributes to mitochondrial loss and cytotoxicity in L02 hepatocytes. Biochem J. 2020 Jun 29;: Authors: Zhang Y, Bian H, Ma Y, Xiao Y, Xiao F Abstract Hexavalent chromium [Cr(VI)] has aroused the main interest of environmental health researchers due to its high toxicity. Liver is the main target organ of Cr(VI), and the purpose of this study was to explore whether mitophagy contributes to Cr(VI)-induced hepatotoxicity and to demonstrate the potential mechanisms. Cr(VI) exposure induced mitochondrial loss, energy metabolism disorders and cell apoptosis, which wer...
Source: The Biochemical Journal - June 28, 2020 Category: Biochemistry Authors: Zhang Y, Bian H, Ma Y, Xiao Y, Xiao F Tags: Biochem J Source Type: research