Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis

Shang, Pan; Meng, Fanling; Liu, Yunduo; Chen, Xiuwei

doi:10.1007/s13277-015-3089-8

Cited by 29 publications

(31 citation statements)

References 18 publications

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“…In order to confirm the expression of ATAD2 in various tumors [11, 16–19], we performed immunohistochemistry analysis on tissue microarrays (TMA) from multiple cancer types including breast, prostate, gastric, colorectal and lung cancers (Figures 1A and Supplementary Figure S1A). ATAD2 was expressed in all tested tumors independent of their tissue of origin.…”

Section: Resultsmentioning

confidence: 99%

“…In cancer cells ATAD2 has been proposed to function as a transcriptional co-regulator of several oncogenic transcriptional factors including estrogen receptor (ER) [12], androgen receptor (AR) [13], E2F transcriptional factor [10] and Myc [14]. Recently, a number of reports have demonstrated that expression of ATAD2 strongly correlates with poor prognosis in different unrelated tumors including gastric cancer [15], endometrial carcinoma [16], hepatocellular carcinoma [17], ovarian carcinoma [18], breast cancer [11, 19] and lung cancer [11] and hence proposed ATAD2 as a poor prognostic marker. Yet it is unclear whether the transcriptional co-regulator function of ATAD2 is the predominant mechanism of malignancy in tumors of diverse origins.…”

Section: Introductionmentioning

confidence: 99%

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ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication

et al. 2016

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ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone di-acetylation-marks during replication.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication

et al. 2016

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“…ATAD2 is overexpressed in a wide variety of cancers, such as colorectal, 25 gastric, 26 endometrial, 27 cervical, 28 and ovarian 29 cancers, in which it increases cell proliferation. Its overexpression is already used as a poor prognosis marker.…”

Section: Bromodomainsmentioning

confidence: 99%

Bromodomain inhibitors and cancer therapy: From structures to applications

2016

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Aberrations in the epigenetic landscape are a hallmark of cancer. Alterations in enzymes that are “writers,” “erasers,” or “readers” of histone modification marks are common. Bromodomains are “readers” that bind acetylated lysines in histone tails. Their most important function is the regulation of gene transcription by the recruitment of different molecular partners. Moreover, proteins containing bromodomains are also epigenetic regulators, although little is known about the specific function of these domains. In recent years, there has been increasing interest in developing small molecules that can target specific bromodomains. First, this has helped clarify biological functions of bromodomain-containing proteins. Secondly, it opens a new front for combatting cancer. In this review we will describe the structures and mechanisms associated with Bromodomain and Extra-Terminal motif (BET) inhibitors and non-BET inhibitors, their current status of development, and their promising role as anti-cancer agents.

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“…Proteins belonging to this family hydrolyse ATP to mediate conformational changes in substrate proteins, resulting in diverse cellular processes 27,28 . ATAD2 plays a key role in cell proliferation and is upregulated as a potential oncogene in cervical, colorectal, breast, and lung cancers [29][30][31][32] . In the budding yeast Saccharomyces cerevisiae, the ATAD2 homologue Yta7 binds to histones and participates in the heterochromatin boundary function in the HMR region, where it counteracts the spread of silencing into the neighbouring euchromatin 33,34 .…”

mentioning

confidence: 99%

Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin

Dong

Oya

Zahedi

et al. 2020

Sci Rep

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Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled is still unclear. Here, we investigate the role of the conserved bromodomain AAA-ATPase, Abo1, involved in maintaining global nucleosome organisation in fission yeast. We identified several key factors involved in heterochromatin silencing that interact genetically with Abo1: histone deacetylase Clr3, H3K9 methyltransferase Clr4, and HP1 homolog Swi6. Cells lacking Abo1 cultivated at 30 °C exhibit an imbalance of H3K9me2 and H3K9me3 in heterochromatin. In abo1∆ cells, the centromeric constitutive heterochromatin has increased H3K9me2 but decreased H3K9me3 levels compared to wild-type. In contrast, facultative heterochromatin regions exhibit reduced H3K9me2 and H3K9me3 levels in abo1∆. Genome-wide analysis showed that abo1∆ cells have silencing defects in both the centromeres and subtelomeres, but not in a subset of heterochromatin islands in our condition. Thus, our work uncovers a role of Abo1 in stabilising directly or indirectly Clr4 recruitment to allow the H3K9me2 to H3K9me3 transition in heterochromatin.In eukaryotic cells, the regions of the chromatin that contain active genes are termed euchromatin, and these regions condense in mitosis to allow for chromosome segregation and decondense in interphase to allow for gene transcription 1 . The chromatin regions that remain condensed throughout the cell cycle are defined as heterochromatin regions and are transcriptionally repressed 2,3 . In general, heterochromatin can be defined molecularly by the modification of histone H3, specifically the absence of methylation on lysine 4 (H3K4me) and presence of methylation on lysine 9 (H3K9me) 4-6 . A conserved group of heterochromatin proteins, the heterochromatin protein 1 (HP1) family, specifically recognise heterochromatin regions by binding to H3K9me. Both di-and tri-methylation (H3K9me2/3) enable the binding of HP1 proteins to silence heterochromatin 7,8 . Heterochromatin regions can be further classified into constitutive and facultative heterochromatin 9,10 . Fission yeast, Schizosaccharomyces pombe, is an excellent model organism for chromatin studies because its heterochromatin organisation is similar to human cells 11,12 . Examples of constitutive heterochromatin regions in S. pombe are the pericentromeric regions that contain repetitive DNA sequences 13 . These regions are regulated by RNAi-dependent silencing machinery that involves protein Dcr1 and Ago1 14,15 . In contrast, the silencing of facultative heterochromatin, such as subtelomeric regions and heterochromatin islands, is mediated by RNAi-independent machinery that can be dynamically modulated to express genes required for the cell cycle or adaptation to the cell environment 16,17 . A subset of facultative heterochromatin islands, known as "determinant of selective removal" (DSR) islands, contain meiotic ...

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Overexpression of ANCCA/ATAD2 in endometrial carcinoma and its correlation with tumor progression and poor prognosis

Cited by 29 publications

References 18 publications

ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication

ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication

Bromodomain inhibitors and cancer therapy: From structures to applications

Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin

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