Does histone acetylation cause cancer?
Altered global levels of histone acetylation, particularly acetylation of H4 at lysine (K)16, have been linked to a cancer phenotype in a variety of cancers (Fraga et al.
Why does histone acetylation might be associated with cancer?
Altered expression and mutations of genes that encode HDACs have been linked to tumor development since they both induce the aberrant transcription of key genes regulating important cellular functions such as cell proliferation, cell-cycle regulation and apoptosis.
What effect does histone deacetylation have on gene expression?
Deacetylation performed by HDAC molecules has the opposite effect. By deacetylating the histone tails, the DNA becomes more tightly wrapped around the histone cores, making it harder for transcription factors to bind to the DNA. This leads to decreased levels of gene expression and is known as gene silencing.
What does histone deacetylases do?
Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues in the NH2 terminal tails of core histones, resulting in a more closed chromatin structure and repression of gene expression.
Which type of cancer is targeted in histone deacetylase inhibitor HDAC therapy?
HDACs seem to be important for gene expression [5]. It has been described several times that their levels vary greatly in cancer cells and differ according to the tumor type. HDAC1 is highly expressed in prostate, gastric, lung, esophageal, colon and breast cancers [6,7,8].
How do histone modifications relate to cancer?
Histone deacetylase inhibitors have pleiotropic effects on cancer cells including growth arrest, apoptosis and differentiation. These effects are linked to transcriptional reactivation of certain genes such as p21, which causes growth arrest (Richon et al, 2000).
How do HDAC inhibitors work in cancer?
HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death. Moreover, they reduce angiogenesis and modulate immune response. Hypothesis of “epigenetic vulnerability of cancer cells”, which has been proposed by Dawson and Kouzarides [38], is a cause of relative specificity of HDAC inhibitors.
What is the function of histone deacetylase inhibitor?
Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells.
What does SIRT1 stand for?
NAD (+)-dependent Class III histone deacetylase SIRT1 is a multiple function protein critically involved in stress responses, cellular metabolism and aging through deacetylating a variety of substrates including p53, forkhead-box transcription factors, PGC-1alpha, NF-kappaB, Ku70 and histones.
What is the role of SIRT1 in colon cancer?
For example, overexpression of SIRT1 in a β-catenin-driven mouse model of colon cancer attenuated tumorigenesis through deacetylation and suppression of β-catenin 23. In addition, SIRT1 knockdown accelerates tumor xenograft formation by HCT116 cells, whereas SIRT1 overexpression suppresses tumor formation 24.
What is the role of SIRT1 in senescence?
The first discovered non-histone target of SIRT1, p53, is suggested to play a central role in SIRT1-mediated functions in tumorigenesis and senescence. SIRT1 was originally considered to be a potential tumor promoter since it negatively regulates the tumor suppressor p53 and other tumor suppressors.
What happens when SIRT1 deacetylates HINT1?
Deacetylation of HINT1 by SIRT1 increases the capacity of HINT1 to bind to β-catenin or MITF. As a result, the tumor-suppressive function of HINT1 is increased.