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117 Newest Publications of Portland Press

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Ubiquitin-C-terminal hydrolases cleave isopeptide and peptide-linked ubiquitin from structured proteins but do not edit ubiquitin homopolymers

09-12-2014 | Bett J; Ritorto M; Ewan R; Jaffray E; Virdee S; Chin J; Knebel A; Kurz T; Trost M; Tatham M; Hay R, Biochemical Journal, 2014

Modification of proteins with ubiquitin (Ub) occurs through a variety of topologically distinct Ub linkages, including Ube2W-mediated monoubiquitylation of N-terminal alpha amines to generate peptide-linked linear mono-Ub fusions. Protein ubiquitylation can be reversed by the action of ...

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Observed bromodomain flexibility reveals histone peptide- and small molecule ligand-compatible forms of ATAD2A.

08-12-2014 | Poncet-Montange G; Zhan Y; Bardenhagen J; Petrocchi A; Leo E; Shi X; Lee IV G; Leonard P; Geck Do M; Cardozo M; Ande ..., Biochemical Journal, 2014

Preventing histone recognition by bromodomains emerges as an attractive therapeutic approach in cancer. Overexpression of ATAD2A in cancer cells is associated with poor prognosis making the bromodomain of ATAD2A a promising epigenetic therapeutic target. In the development of an in vitro assay ...

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The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex

01-12-2014 | Abdul Azeez KR; Knapp S; Fernandes JMP; Klussmann E; Elkins JM, Biochemical Journal, 2014

The RhoGEF (Rho GTPase guanine-nucleotide-exchange factor) domain of AKAP-Lbc (A-kinase-anchoring protein-Lbc, also known as AKAP13) catalyses nucleotide exchange on RhoA and is involved in the development of cardiac hypertrophy. The RhoGEF activity of AKAP-Lbc has also been implicated in cancer. ...

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Identification of key binding site residues of MCT1 for AR-C155858 reveals the molecular basis of its isoform selectivity

01-12-2014 | Nancolas B; Sessions R; Halestrap A, Biochemical Journal, 2014

The proton-linked monocarboxylate transporters (MCTs) are required for lactic acid transport into all mammalian cells. Thus they play an essential role in tumour cells that are usually highly glycolytic and are promising targets for anti-cancer drugs. AR-C155858 is a potent MCT1 inhibitor (Ki ~ 2 ...

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Ubiquitination profiling identifies sensitivity factors for IAP antagonist treatment

21-11-2014 | Varfolomeev E; Izrael-Tomasevic A; Yu K; Bustos D; Goncharov T; Belmont L; Masselot A; Bakalarski C; Kirkpatrick D; ..., Biochemical Journal, 2014

Evasion of cell death is one crucial capability acquired by tumor cells to ward off anti-tumor therapies, and represents a fundamental challenge to sustaining clinical efficacy for currently available agents. Inhibitor of Apoptosis (IAP) proteins use their ubiquitin E3 ligase activity to promote ...

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Epithelial MUC1/Muc1 Promotes Cell migration, Reduces Apoptosis and Affects Levels of Mucosal Modulators During Acetylsalicylic Acid (Aspirin) Induced Gastropathy.{Less than}i{Greater than}{Less than}/i{Greater than}

11-11-2014 | Banerjee D; Fernandez H; Patil P; Premaratne P; Quiding-J{a}rbrink M; Lind{e}n S, Biochemical Journal, 2014

MUC1 is a transmembrane mucin highly expressed in the stomach. While extensive research has uncovered many of its roles in cancer, knowledge about the functions of MUC1 in normal tissues is limited. Here we showed that acetylsalicylic acid (Aspirin, ASA) upregulated MUC1/Muc1 expression in the ...

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The clinically-approved drugs Dasatinib and Bosutinib induce anti-inflammatory macrophages by inhibiting the Salt-Inducible Kinases

29-10-2014 | Ozanne J; Prescott A; Clark K, Biochemical Journal, 2014

Macrophages switch to an anti-inflammatory, ‘regulatory’-like phenotype characterized by the production of high levels of IL-10 and low levels of pro-inflammatory cytokines to promote the resolution of inflammation. A potential therapeutic strategy for the treatment of chronic inflammatory ...

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Bioenergetic differences between MCF-7 and T47D breast cancer cells and their regulation by estradiol and tamoxifen

03-10-2014 | Radde B; Ivanova M; Mai H; Salabei J; Hill B; Klinge C, Biochemical Journal, 2014

Estrogen receptor α (ERα+) breast tumors rely on mitochondria (mt) to generate ATP. The goal of this study was to determine how estradiol (E2) and 4-hydroxytamoxifen (4-OHT) affect cellular bioenergetic function in MCF-7 and T47D ERα+ breast cancer cells in serum-replete versus dextran-coated ...

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DNA polymerase eta is regulated by poly(rC)-binding protein 1 via mRNA stability

30-09-2014 | Ren C; Cho S; Jung Y; Chen X, Biochemical Journal, 2014

DNA polymerase eta (POLH), a target of p53 tumor suppressor, plays a key role in translesion DNA synthesis (TLS). Loss of POLH is responsible for human cancer prone syndrome, Xeroderma Pigmentosum Variant (XPV). Due to its critical role in DNA repair and genome stability, POLH expression and ...

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Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria

15-09-2014 | Bridges HR; Jones AJY; Pollak MN; Hirst J, Biochemical Journal, 2014

The biguanide metformin is widely prescribed for TypeII diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by metformin is the primary cause of its cell-lineage-specific actions and therapeutic effects, the ...

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