Olzscha, Heidi, Bekheet, Mina E, Sheikh, Semira, La Thangue, Nicholas B, Heidi Olzscha, Mina E. Bekheet, Semira Sheikh, Nicholas B. La Thangue, Bekheet, Mina E., Thangue, Nicholas B. La
Abstract
Lysine acetylation in proteins is one of the most abundant posttranslational modifications in eukaryotic cells. The dynamic homeostasis of lysine acetylation and deacetylation is dictated by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). Important substrates for HATs and HDACs are histones, where lysine acetylation generally leads to an open and transcriptionally active chromatin conformation. Histone deacetylation forces the compaction of the chromatin with subsequent inhibition of transcription and reduced gene expression. Unbalanced HAT and HDAC activity, and therefore aberrant histone acetylation, has been shown to be involved in tumorigenesis and progression of malignancy in different types of cancer. Therefore, the development of HDAC inhibitors (HDIs) as therapeutic agents against cancer is of great interest. However, treatment with HDIs can also affect the acetylation status of many other non-histone proteins which play a role in different pathways including angiogenesis, cell cycle progression, autophagy and apoptosis. These effects have led HDIs to become anticancer agents, which can initiate apoptosis in tumor cells. Hematological malignancies in particular are responsive to HDIs, and four HDIs have already been approved as anticancer agents. There is a strong interest in finding adequate biomarkers to predict the response to HDI treatment. This chapter provides information on how to assess HDAC activity in vitro and determine the potency of HDIs on different HDACs. It also gives information on how to analyze cellular markers following HDI treatment and to analyze tissue biopsies from HDI-treated patients. Finally, a protocol is provided on how to detect HDI sensitivity determinants in human cells, based on a pRetroSuper shRNA screen upon HDI treatment.
Pharmacology, Toxicology and Pharmaceutical Science
3
6%
Other
8
16%
Unknown
12
24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 June 2016.
All research outputs
#18,461,618
of 22,875,477 outputs
Outputs from Methods in molecular biology
#7,923
of 13,131 outputs
Outputs of similar age
#284,555
of 393,698 outputs
Outputs of similar age from Methods in molecular biology
#846
of 1,471 outputs
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So far Altmetric has tracked 13,131 research outputs from this source. They receive a mean Attention Score of 3.4. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
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We're also able to compare this research output to 1,471 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
