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Institution

Laboratory of Molecular Biology

FacilityCambridge, Cambridgeshire, United Kingdom
About: Laboratory of Molecular Biology is a facility organization based out in Cambridge, Cambridgeshire, United Kingdom. It is known for research contribution in the topics: Gene & RNA. The organization has 19395 authors who have published 24236 publications receiving 2101480 citations.
Topics: Gene, RNA, DNA, Population, Transcription (biology)


Papers
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Journal ArticleDOI
31 Mar 2016-Nature
TL;DR: A new mechanism by which the antitumour response of mouse CD8+ T cells can be potentiated by modulating cholesterol metabolism is reported, which indicates ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.
Abstract: CD8(+) T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment. Reactivating the cytotoxicity of CD8(+) T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8(+) T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme, led to potentiated effector function and enhanced proliferation of CD8(+) but not CD4(+) T cells. This is due to the increase in the plasma membrane cholesterol level of CD8(+) T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8(+) T cells were better than wild-type CD8(+) T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.

580 citations

Journal ArticleDOI
TL;DR: Crystallized Lys 63‐linked and linear ubiquitin dimers are revealed, revealing that both adopt equivalent open conformations, forming no contacts between Ubiquitin molecules and thereby differing significantly from Lys 48‐linked ubiquitIn chains.
Abstract: At least eight types of ubiquitin chain exist, and individual linkages affect distinct cellular processes. The only distinguishing feature of differently linked ubiquitin chains is their structure, as polymers of the same unit are chemically identical. Here, we have crystallized Lys 63-linked and linear ubiquitin dimers, revealing that both adopt equivalent open conformations, forming no contacts between ubiquitin molecules and thereby differing significantly from Lys 48-linked ubiquitin chains. We also examined the specificity of various deubiquitinases (DUBs) and ubiquitin-binding domains (UBDs). All analysed DUBs, except CYLD, cleave linear chains less efficiently compared with other chain types, or not at all. Likewise, UBDs can show chain specificity, and are able to select distinct linkages from a ubiquitin chain mixture. We found that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO (NF-κB essential modifier) binds to linear chains exclusively, whereas the NZF (Npl4 zinc finger) domain of TAB2 (TAK1 binding protein 2) is Lys 63 specific. Our results highlight remarkable specificity determinants within the ubiquitin system.

578 citations

Journal ArticleDOI
TL;DR: The overall quaternary structure of oxyhaemoglobin is identical, within experimental error, to that of carbon monoxide haemoglobin, and thus confirms the applicability of the allosteric mechanisms proposed by Perutz and Baldwin & Chothia to the process of oxygen binding.

578 citations

Journal ArticleDOI
01 Nov 1975-Cell
TL;DR: The results suggest that alpha-actinin may be involved in the organization ofActin filament bundles, in the attachment of actin filaments to the plasma membrane, and in the assembly of actIn filaments in areas of cell to cell contact.

577 citations

Journal ArticleDOI
05 Aug 1983-Science
TL;DR: Tissue culture cells from several mammalian species, including three primate lines, were transfected with recombinant vectors carrying Escherichia coli xanthine-guanine phosphoribosyltransferase or Tn5 aminoglycoside phosphotransferase dominant selectable markers to establish stable transformation frequencies.
Abstract: Tissue culture cells from several mammalian species, including three primate lines, were transfected with recombinant vectors carrying Escherichia coli xanthine-guanine phosphoribosyltransferase or Tn5 aminoglycoside phosphotransferase dominant selectable markers. Human HeLa and SV40-transformed xeroderma pigmentosum cells exhibited stable transformation frequencies of at least 10(-3) (0.1 percent). CV-1, an African green monkey kidney cell line, could be stably transformed with the exceptionally high frequency of 6 X 10(-2) (6 percent).

577 citations


Authors

Showing all 19431 results

NameH-indexPapersCitations
Robert J. Lefkowitz214860147995
Ronald M. Evans199708166722
Tony Hunter175593124726
Marc G. Caron17367499802
Mark Gerstein168751149578
Timothy A. Springer167669122421
Harvey F. Lodish165782101124
Ira Pastan1601286110069
Bruce N. Ames158506129010
Philip Cohen154555110856
Gerald M. Rubin152382115248
Ashok Kumar1515654164086
Kim Nasmyth14229459231
Kenneth M. Yamada13944672136
Harold E. Varmus13749676320
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20239
202265
20211,222
20201,165
20191,082
2018945