Cytoplasmic DRAK1 overexpressed in head and neck cancers inhibits TGF-β1 tumor suppressor activity by binding to Smad3 to interrupt its complex formation with Smad4

Park, Y; Kim, W; Lee, Jang-Ming; Park, J; Cho, J K; Pang, Kyoungwha; Lee, J; Kim, D; Sw, Park; Yang, Kun; Sj, Kim

doi:10.1038/onc.2014.423

Cited by 30 publications

(29 citation statements)

References 33 publications

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“…Thus, DAPK3 activation could be a possible novel strategy for treatment of prostate cancer that could be synergized if combined with Akt inhibitors. Additionally, DAPK3 is mutated or methylated in many cancers, allowing the cancer cells to attenuate DAPK3's apoptotic tumor suppressor functions …”

Section: Dapks Cellular Functionsmentioning

confidence: 99%

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Farag

Roh

2018

Medicinal Research Reviews

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Serine/threonine kinases (STKs) represent the majority of discovered kinases to date even though a few Food and Drug Administration approved STKs inhibitors are reported. The third millennium came with the discovery of an important group of STKs that reshaped our understanding of several biological signaling pathways. This family was named death-associated protein kinase family (DAPK family). DAPKs comprise five members (DAPK1, DAPK2, DAPK3, DRAK1, and DRAK2) and belong to the calcium/calmodulin-dependent kinases domain. As time goes on, the list of biological functions of this family is constantly updated. The most extensively studied member is DAPK1 (based on the publications number and Protein Data Bank reported crystal structures) that plays fundamental biological roles depending on the cellular context. DAPK1 regulates apoptosis, autophagy, contributes to the pathogenesis of Alzheimer's disease, acts as a tumor suppressor, inhibits metastasis, mediates the body responses to viral infections, and regulates the synaptic plasticity and depression. For their biological roles, several DAPKs' modulators have been reported for treatment of many diseases as well as acting as probe compounds to facilitate the understanding of the biological functions elicited by this family. Despite that, the number of reported modulators is still limited and more research needs to be conducted on the discovery of novel strategies to activate or inhibit this family. In this report, we aim at drawing more attention to this family by reviewing the recent updates regarding the structure, biological roles, and regulation of this family. In addition, the small-molecule modulators of this family are reviewed in details with their potential therapeutic outcomes evaluated to help medicinal chemists develop more potent and selective possible drug candidates.

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Section: Dapks Cellular Functionsmentioning

confidence: 99%

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Farag

Roh

2018

Medicinal Research Reviews

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“…GO: 0071146 (SMAD3-SMAD4 protein complex) turns out to be a significant indicator for essential genes. According to recent publications, this CC GO term has been validated to contribute to the transforming growth factor-beta signaling pathway, which further participates in the proliferation, survival and transformation of normal and malignant somatic cells, including leukemia cells [ 80 , 81 ].…”

Section: Resultsmentioning

confidence: 99%

Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways

et al. 2017

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Identifying essential genes in a given organism is important for research on their fundamental roles in organism survival. Furthermore, if possible, uncovering the links between core functions or pathways with these essential genes will further help us obtain deep insight into the key roles of these genes. In this study, we investigated the essential and non-essential genes reported in a previous study and extracted gene ontology (GO) terms and biological pathways that are important for the determination of essential genes. Through the enrichment theory of GO and KEGG pathways, we encoded each essential/non-essential gene into a vector in which each component represented the relationship between the gene and one GO term or KEGG pathway. To analyze these relationships, the maximum relevance minimum redundancy (mRMR) was adopted. Then, the incremental feature selection (IFS) and support vector machine (SVM) were employed to extract important GO terms and KEGG pathways. A prediction model was built simultaneously using the extracted GO terms and KEGG pathways, which yielded nearly perfect performance, with a Matthews correlation coefficient of 0.951, for distinguishing essential and non-essential genes. To fully investigate the key factors influencing the fundamental roles of essential genes, the 21 most important GO terms and three KEGG pathways were analyzed in detail. In addition, several genes was provided in this study, which were predicted to be essential genes by our prediction model. We suggest that this study provides more functional and pathway information on the essential genes and provides a new way to investigate related problems.

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“…On the other hand, up-regulated STK17A in glioblastomas has been reported, where it was associated with tumor grade and patient survival [ 30 ]. Moreover, STK17A has been found to be overexpressed in human head and neck squamous cell carcinoma by inhibiting the tumor suppressive activity of transforming growth factor (TGF)-beta signaling [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early Sign of Chronic Rejection

et al. 2015

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The biological significance of STK17A, a serine/threonine kinase, in the liver is not known. We analyzed STK17A expression in HepG2 cells and human liver tissue. Accordingly, we investigated whether STK17A could help in identifying earlier changes during the evolution of chronic rejection (CR) after liver transplantation. RT-PCR and immunofluorescence were used to analyze STK17A expression in HepG2 cells. Antibody microarray was performed using human liver samples from CR and healthy donors. Immunohistochemistry was used to verify the clinical utility of STK17A on sequential biopsies for the subsequent development of CR. A novel short isoform of STK17A was found in HepG2 cells. STK17A was localized in the nuclei and bile canaliculi in HepG2 cells and human livers. Microarray of STK17A revealed its decrease in failed liver allografts by CR. During the evolution of CR, the staining pattern of bile canalicular STK17A gradually changed from diffuse linear to focal intermittent. The focal intermittent staining pattern was observed before the definite diagnosis of CR. In conclusion, the present study was the first to find localization of STK17A in normal bile canaliculi. Abnormal expression and localization of STK17A were associated with CR of liver allografts since the early stage of the rejection process.

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Cytoplasmic DRAK1 overexpressed in head and neck cancers inhibits TGF-β1 tumor suppressor activity by binding to Smad3 to interrupt its complex formation with Smad4

Cited by 30 publications

References 33 publications

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways

Abnormal Localization of STK17A in Bile Canaliculi in Liver Allografts: An Early Sign of Chronic Rejection

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