The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy.
Guo Li,Yuan Tian,Wei-Guo Zhu +2 more
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TLDR
This review detailing the diverse structures of HDACs and their underlying biological functions, including transcriptional regulation, metabolism, angiogenesis, DNA damage response, cell cycle, apoptosis, protein degradation, immunity and other several physiological processes, highlights potential avenues to use HDACi as novel, precision cancer treatments.Abstract:
Genetic mutations and abnormal gene regulation are key mechanisms underlying tumorigenesis. Nucleosomes, which consist of DNA wrapped around histone cores, represent the basic units of chromatin. The fifth amino group (Ne) of histone lysine residues is a common site for post-translational modifications (PTMs), and of these, acetylation is the second most common. Histone acetylation is modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), and is involved in the regulation of gene expression. Over the past two decades, numerous studies characterizing HDACs and HDAC inhibitors (HDACi) have provided novel and exciting insights concerning their underlying biological mechanisms and potential anti-cancer treatments. In this review, we detail the diverse structures of HDACs and their underlying biological functions, including transcriptional regulation, metabolism, angiogenesis, DNA damage response, cell cycle, apoptosis, protein degradation, immunity and other several physiological processes. We also highlight potential avenues to use HDACi as novel, precision cancer treatments.read more
Citations
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The epigenetics of epithelial-mesenchymal plasticity in cancer
Wai Leong Tam,Robert A. Weinberg +1 more
TL;DR: In this article, a review of the interactions between EMT-inducing transcription factors and epigenetic modulators during cancer progression and the therapeutic implications of exploiting this intricate regulatory process is presented.
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Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.
TL;DR: In this article, the authors shed new light on recent advances in the biological characteristics and immunosuppressive functions of myeloid-derived suppressor cells (MDSCs) and proposed an overview of current MDSCs-targeting therapies so as to provide new ideas for cancer treatment.
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The role of histone modifications: from neurodevelopment to neurodiseases
TL;DR: A growing body of evidence suggests that epigenetic mechanisms, such as histone modifications, allow the fine-tuning and coordination of spatiotemporal gene expressions during neurogenesis as mentioned in this paper .
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Discovering the landscape of protein modifications.
TL;DR: Protein modifications modulate nearly every aspect of cell biology in organisms, ranging from Archaea to Eukaryotes as discussed by the authors, and new computational tools in data science, machine learning, and artificial intelligence are poised to allow researchers to make significant progress in discovering new protein modifications and determining their function.
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Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention
Dusan Ruzic,Nemanja Djokovic,Tatjana Srdic-Rajic,Cesar Echeverria,K. Nikolics,Juan F. Santibanez +5 more
TL;DR: The small-molecules and natural products such as HDACi are described in terms of cancer therapy and chemoprevention and structural considerations are included to improve theHDACi selectivity and combinatory potential with other specific targeting agents in bifunctional inhibitors and proteolysis targeting chimeras.
References
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Journal ArticleDOI
Translating the Histone Code
Thomas Jenuwein,C. David Allis +1 more
TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Journal ArticleDOI
The language of covalent histone modifications.
Brian D. Strahl,C D Allis +1 more
TL;DR: It is proposed that distinct histone modifications, on one or more tails, act sequentially or in combination to form a ‘histone code’ that is, read by other proteins to bring about distinct downstream events.
Journal ArticleDOI
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
Journal ArticleDOI
Crystal structure of the nucleosome core particle at 2.8 Å resolution
TL;DR: The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it.
Journal ArticleDOI
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Anne Brunet,Azad Bonni,Michael J. Zigmond,Michael Z. Lin,Peter Juo,Linda Hu,Michael J. Anderson,Karen C. Arden,John Blenis,Michael E. Greenberg +9 more
TL;DR: It is demonstrated that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors, which triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.
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