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124 Newest Publications of Portland Press

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Targeting Cullin-RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation

01-May-2015 | Bulatov E; Ciulli A, Biochemical Journal, 2015

In the last decade, the ubiquitin-proteasome system has emerged as a valid target for the development of novel therapeutics. E3 ubiquitin ligases are particularly attractive targets because they confer substrate specificity on the ubiquitin system. CRLs [Cullin-RING (really interesting new gene) ...

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

15-Mar-2015 | Bett JS; Ritorto MS; Ewan R; Jaffray EG; Virdee S; Chin JW; Knebel A; Kurz T; Trost M; Tatham MH; Hay RT, Biochemical Journal, 2015

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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Iron alters cell survival in a mitochondria-dependent pathway in ovarian cancer cells

01-Mar-2015 | Bauckman K; Haller E; Taran N; Rockfield S; Ruiz-Rivera A; Nanjundan M, Biochemical Journal, 2015

The role of iron in the development of cancer remains unclear. We previously reported that iron reduces cell survival in a Ras/mitogen-activated protein kinase (MAPK)-dependent manner in ovarian cells; however, the underlying downstream pathway leading to reduced survival was unclear. Although ...

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PT-1 selectively activates AMPK-{gamma}1 complexes in mouse skeletal muscle, but activates all three {gamma} subunit complexes in cultured human cells by inhibiting the respiratory chain

19-Feb-2015 | Jensen T; Ross F; Kleinert M; Sylow L; Knudsen J; Gowans G; Hardie D; Richter E, Biochemical Journal, 2015

AMP-activated protein kinase (AMPK) occurs as heterotrimeric complexes in which a catalytic subunit (α1/α2) is bound to one of two b subunits (β1/β2) and one of three γ subunits (γ1/γ2/γ3). The ability to selectively activate specific isoforms would be a useful research tool, and a promising ...

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Small Molecule Inhibitors of ERK-mediated Immediate Early Gene Expression and Proliferation of Melanoma Cells Expressing Mutated BRaf

19-Feb-2015 | Samadani R; Zhang J; Brophy A; Oashi T; Priyakumar U; Raman E; St. John F; Jung K; Fletcher S; Pozharski E; MacKerel ..., Biochemical Journal, 2015

Constitutive activation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) are central to regulating the proliferation and survival of many cancer cells. The current inhibitors of ERK1/2 target ATP binding or the catalytic site and are therefore limited in their utility for ...

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The clinically approved drugs dasatinib and bosutinib induce anti-inflammatory macrophages by inhibiting the salt-inducible kinases

15-Jan-2015 | Ozanne J; Prescott AR; Clark K, Biochemical Journal, 2015

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

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The solution structure of the MANEC-type domain from Hepatocyte Growth Factor Activator Inhibitor 1 reveals an unexpected PAN/apple domain-type fold.

16-Dec-2014 | Hong Z; Nowakowski M; Spronk C; Petersen S; Andreasen P; Ko{z}mi{n}ski W; Mulder F; Jensen J, Biochemical Journal, 2014

A decade ago, a Motif at N-terminus with Eight-Cysteines or in short MANEC was defined as a new protein domain family. This domain is found exclusively in the N-terminus of >400 multi-domain type-1 transmembrane proteins from animals. Despite the large number of MANEC-containing proteins, only ...

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

09-Dec-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-Dec-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-Dec-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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