Low Proteolytic Clipping of Histone H3 in Cervical Cancer

Sandoval-Basilio, Jorge; Serafín-Higuera, Nicolás; Reyes-Hernández, Octavio Daniel; Serafín-Higuera, Idanya; Leija-Montoya, Gabriela; Blanco-Morales, Magali; Sierra-Martínez, Mónica; Ramos-Mondragón, Roberto; García, Silvia; López-Hernández, Luz Berenice; Yocupicio-Monroy, Martha; Alcaráz-Estrada, Sofía Lizeth

doi:10.7150/jca.15605

Cited by 9 publications

(15 citation statements)

References 19 publications

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“…Acetylation, especially histone acetylation, plays a role in regulating gene expression . Alteration of histone 3 and 4 acetylation level has been observed in a variety of cancers, including cervical cancer . Histone deacetylase 1 (HDAC1) and HDAC2 are up‐regulated in cervical dysplasia and invasive cervical carcinoma .…”

Section: Introductionmentioning

confidence: 99%

“…9 Alteration of histone 3 and 4 acetylation level has been observed in a variety of cancers, including cervical cancer. 10,11 Histone deacetylase 1 (HDAC1) and HDAC2 are up-regulated in cervical dysplasia and invasive cervical carcinoma. 12 In cervical cancer HeLa cells, down-regulation of HDAC2 expression inhibited cell proliferation and induced cell cycle arrest.…”

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confidence: 99%

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The lysine acetyltransferase GCN5 contributes to human papillomavirus oncoprotein E7‐induced cell proliferation via up‐regulating E2F1

Qiao

Zhang

et al. 2018

J Cellular Molecular Medi

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General control nondepressible 5 (GCN5), the first identified transcription‐related lysine acetyltransferase (KAT), is an important catalytic component of a transcriptional regulatory SAGA (Spt‐Ada‐GCN5‐Acetyltransferase) and ATAC (ADA2A‐containing) complex. While GCN5 has been implicated in cancer development, its role in cervical cancer is not known. The human papillomavirus (HPV) oncoprotein E7 abrogates the G1 cell cycle checkpoint and induces genomic instability, which plays a central role in cervical carcinogenesis. In this study, we observed that GCN5 was up‐regulated in HPV E7‐expressing cells, knockdown of GCN5 inhibited cell cycle progression and DNA synthesis in HPV E7‐expressing cells. Notably, GCN5 knockdown reduced the steady‐state levels of transcription factor E2F1. Depletion of E2F1 caused G1 arrest while overexpression of E2F1 rescued the inhibitory effects of GCN5 knockdown on G1/S progression in HPV E7‐expressing cells. Results from chromatin immunoprecipitation (ChIP) assays demonstrated that GCN5 bound to the E2F1 promoter and increased the extent of histone acetylation within these regions. GCN5 also acetylated c‐Myc and increased its ability to bind to the E2F1 promoter. Knockdown of c‐Myc reduced the steady‐state levels of E2F1 and caused G1 arrest. These results revealed a novel mechanism of E7 function whereby elevated GCN5 acetylates histones and c‐Myc to regulate E2F1 expression and cell cycle progression.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

The lysine acetyltransferase GCN5 contributes to human papillomavirus oncoprotein E7‐induced cell proliferation via up‐regulating E2F1

Qiao

Zhang

et al. 2018

J Cellular Molecular Medi

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“…During the different stages of cervical cancer development, there is an accumulation of epigenetic alterations that leads to changes in gene expression [8]. Altered mechanisms of epigenetic regulation in cervical cancer include DNA methylation and post-translational modifications of histone proteins [8].…”

Section: Introductionmentioning

confidence: 99%

“…Altered mechanisms of epigenetic regulation in cervical cancer include DNA methylation and post-translational modifications of histone proteins [8]. It has been reported that histone modifying enzymes such as histone deacetylase (HDAC)-1 and HDAC2 are over-expressed in cervical dysplasia and invasive carcinoma [9].…”

Section: Introductionmentioning

confidence: 99%

Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer

Beyer

Zhu

Mayr

et al. 2017

IJMS

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Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology.

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“…Recently, this method has also been used to study histone proteolysis [84]. As previously discussed, histone proteolysis has been reported to influence gene expression during cell differentiation, and has also been observed in cancer cell lines [46, 85]. Thus, understanding histone proteolysis can elucidate the pathologies of some diseases such as cervical cancer where histone proteolysis has also been reported [84].…”

Section: Analyzing In Vivo Proteolysis With Middle-down and Top-domentioning

confidence: 99%

Monitoring proteolytic processing events by quantitative mass spectrometry

Coradin

Karch

Garcia

2017

Expert Review of Proteomics

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Introduction Protease activity plays a key role in a wide variety of biological processes including gene expression, protein turnover and development. Misregulation of these proteins has been associated with many cancer types such as prostate, breast, and skin cancer. Thus, the identification of protease substrates will provide key information to understand proteolysis-related pathologies. Areas covered Proteomics-based methods to investigate proteolysis activity, focusing on substrate identification, protease specificity and their applications in systems biology are reviewed. Their quantification strategies, challenges and pitfalls are underlined and the biological implications of protease malfunction are highlighted. Expert commentary Dysregulated protease activity is a hallmark for some disease pathologies such as cancer. Current biochemical approaches are low throughput and some are limited by the amount of sample required to obtain reliable results. Mass spectrometry (MS) based proteomics provides a suitable platform to investigate protease activity, providing information about substrate specificity and mapping cleavage sites.

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Low Proteolytic Clipping of Histone H3 in Cervical Cancer

Cited by 9 publications

References 19 publications

The lysine acetyltransferase GCN5 contributes to human papillomavirus oncoprotein E7‐induced cell proliferation via up‐regulating E2F1

The lysine acetyltransferase GCN5 contributes to human papillomavirus oncoprotein E7‐induced cell proliferation via up‐regulating E2F1

Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer

Monitoring proteolytic processing events by quantitative mass spectrometry

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