Chemical synthesis of the ATAD2 bromodomain

Creech, Gardner S.; Paresi, Chelsea; Li, Yueming

doi:10.1073/pnas.1400556111

Cited by 16 publications

(16 citation statements)

References 45 publications

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“…Discovery of the ATAD2 gene is a new breakthrough in oncology research. The AAA+ ATPase structure domain is a molecular chaperone using ATP activity to participate in the activities of cells, cell cycle control, signal transduction, and gene expression regulation (15). The bromine structure domain and acetylation of the lysine model adjust chromosome remodeling and transcriptional control of the interaction between proteins (16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Zheng

Zhang

et al. 2015

Oncology Reports

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The ATPase family AAA domain-containing protein 2 (ATAD2) is associated with many cellular processes, such as cell proliferation, invasion and migration. However, the molecular biological function of the ATAD2 gene in cervical cancer is unclear. The purpose of this study was to explore ATAD2 expression in cervical cancer, evaluate the relationship between the development of cervical cancer, metastasis and clinicopathological characteristics, and discuss the implications for its use in clinical treatment. Protein and mRNA expression of ATAD2 was examined in tissues and cell lines. Tumor tissues from 135 cases of cervical cancer were collected for evaluation of ATAD2 expression by immunohistochemistry and western blotting. Prognostic significance was evaluated by the Cox hazards model and Kaplan-Meier survival method. HeLa and SiHa cells were transfected with two siRNAs targeting ATAD2. ATAD2 knockdown was used to analyze cell proliferation, invasion and migration. Cell viability was evaluated with the Cell Counting Κit-8 (CCK-8) assay, cell invasion by a Transwell assay and cell migration by a wound healing/scratch migration assay. ATAD2 was shown to be highly expressed in cervical cancer tissues, both at the transcriptional and protein levels, and was correlated with poor patient survival (P<0.05). Knockdown of ATAD2 in the HeLa and SiHa cells was found to reduce the capacity for invasion and migration (P<0.05), and inhibited the growth and clonogenic potential of the HeLa and SiHa cell lines. Our results suggest that cervical cancer tissues may have highly expressed ATAD2, which is associated with tumor stage and lymph node status (P<0.05). Oncogene ATAD2 may play an important role in cervical cancer proliferation, invasion and migration. It could serve as a prognostic marker and a therapeutic target for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Zheng

Zhang

et al. 2015

Oncology Reports

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“…In addition, we and others have shown that increased ATAD2 may predict survival, and we here confirm that ATAD2 protein assessed by IHC is an independent prognostic marker in endometrioid endometrial cancer patients. Combined with the increased efforts to target bromodomain-containing proteins in cancer [ 15 , 26 ], ATAD2 seems an attractive cancer protein for more detailed studies. It is also interesting that our molecular analyses point to PI3K-pathway and HDAC inhibitors as potential drugs for treatment of patients with high ATAD2.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to its N-terminal part that interacts with E2F and AR, ATAD2 consists of a bromodomain capable of binding to acetylated histones, and the AAA ATPase domain that possesses ATPase activity and mediates protein multimerization [ 4 , 5 , 13 ]. Both the bromodomain and the AAA ATPase domain could be targeted by small molecule inhibitors, and the recent chemical synthesis of the ATAD2 bromodomain could facilitate further studies of the function of the protein [ 15 ]. Combined with its apparent wide overexpression in cancers, this leaves ATAD2 as a promising target for therapy in several cancers and calls for further investigations of its expression in specific cancer types.…”

Section: Introductionmentioning

confidence: 99%

ATAD2 overexpression links to enrichment of B-MYB-translational signatures and development of aggressive endometrial carcinoma

et al. 2015

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We have explored the potential for clinical implementation of ATAD2 as a biomarker for aggressive endometrial cancer by investigating to what extent immunohistochemical (IHC) staining for ATAD2 is feasible, reflects clinical phenotype and molecular subgroups of endometrial carcinomas. Increased expression of the ATAD2 gene has been implicated in cancer development and progression in a number of tissues, but few studies have investigated ATAD2 expression using IHC. Here we show that high ATAD2 protein expression is significantly associated with established clinical-pathological variables for aggressive endometrial cancer, also in the subset of estrogen receptor α (ERα) positive tumors. Protein and mRNA expression of ATAD2 were highly correlated (P < 0.001), suggesting that IHC staining may represent a more clinically applicable measure of ATAD2 level in routinely collected formalin fixed paraffin embedded specimens. Gene expression alterations in samples with high ATAD2 expression revealed upregulation of several cancer-related genes (B-MYB, CDCs, E2Fs) and gene sets that previously have been linked to aggressive disease and potential for new targeting therapies. Our results support that IHC staining for ATAD2 may be a clinically applicable biomarker reflecting clinical phenotype and targetable alterations in endometrial carcinomas to be further explored in controlled clinical trials.

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“…Danishefsky's group then applied this approach to the chemical synthesis of hPTHrP and ATAd2 [80,81]. hPTHrP is a protein widespread in human tissues.…”

Section: Ligation At Leucine Sitementioning

confidence: 99%

“…This 130-mer peptide was assembled from five fragments via one Cys-ligation and three Leu-ligations in a highly convergent manner with only three total RP-HPLC events. The global desulfurization was also achieved under metalfree conditions [81].…”

Section: Ligation At Leucine Sitementioning

confidence: 99%

Postligation-Desulfurization: A General Approach for Chemical Protein Synthesis

Zeng

Wan

2014

Topics in Current Chemistry

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Native chemical ligation, involving regioselective and chemoselective coupling of two unprotected peptide segments, enabled the synthesis of polypeptide with more than 200 amino acids. However, cysteine was indispensable in this synthetic technique in its initial format, which limited its further application. Thus, considerable effort has been put into breaking the restriction of cysteine-containing ligation. As a consequence, postligation-desulfurization, concerning thiol-mediated ligation followed by desulfurization, was developed. This review describes the development and recent progress on the chemical synthesis of peptides and proteins encompassing postligation-desulfurization at alanine, valine, lysine, threonine, leucine, proline, arginine, aspartic acid, glutamate, phenylalanine, glutamine, and tryptophan.

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Chemical synthesis of the ATAD2 bromodomain

Cited by 16 publications

References 45 publications

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

Oncogene ATAD2 promotes cell proliferation, invasion and migration in cervical cancer

ATAD2 overexpression links to enrichment of B-MYB-translational signatures and development of aggressive endometrial carcinoma

Postligation-Desulfurization: A General Approach for Chemical Protein Synthesis

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