Accumulation of hypoxia-inducible factor-1 is limited by transcription-dependent depletion. Zoya N Demidenko

Accumulation of hypoxia-inducible factor-1 is limited by transcription-dependent depletion

Abstract
In the presence of oxygen and iron, hypoxia-inducible factor (HIF-1alpha) is rapidly degraded via the prolyl hydroxylases (PHD)/VHL pathways. Given striking similarities between p53 and HIF-1alpha regulation, we previously suggested that HIF-1 transcriptionally initiates its own degradation and therefore inhibitors of transcription must induce HIF-1alpha. Under normoxia, while inducing p53, inhibitors of transcription did not induce HIF-1alpha. Under hypoxia or low iron (DFX), inhibitors of transcription dramatically super-induced HIF-1alpha. Removal of inhibitors resulted in outburst of the HIF-1-dependent transcription followed by depletion of HIF-1alpha. Although hypoxia/DFX induced PHD3, we excluded the PHD/VHL pathway in the regulation of HIF-1alpha under hypoxia/DFX. The transcription-dependent degradation of HIF-1alpha under hypoxia occurs via the proteasome and is accelerated by protein acetylation. Thus, HIF-1alpha is regulated by two distinct mechanisms. Under normoxia, HIF-1alpha is degraded via the classic PHD/VHL pathway, is expressed at low levels and therefore does not activate the feedback loop. But under hypoxia, HIF-1alpha accumulates and transcriptionally activates its own degradation that is independent from the PHD/VHL pathway. https://www.researchgate.net/scientific-contributions/39445053_Zoya_N_Demidenko


oncotarget removed from pubmed Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .


When general population discuss today’s medicine, accuracy plays one of the most crucial roles and people’s lives are literally dependent on it. Likewise, any researches pertaining to medicine are necessary to meet the highest standards. The challenge today is that any outcomes of researches can be posted online and used as a reference without being thoroughly checked and validated. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and decided to generate an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The major principle of this journal is based on Altmetric scores that are used as a quality indicator. That allows both readers and authors to quality-check publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with respective scores above 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the required help to anybody, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was released back in 2018 by Oncotarget and written by different experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are aiming to understand the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Likewise, the publication about melanoma, was used for citations in different news articles 69 times. In addition, it was referred to in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
Another Oncotarget’s research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is glad to have the chance to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
http://vivo.med.cornell.edu/display/journal1949-2553

Comments

Post a Comment

Popular posts from this blog

Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer

Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer ABSTRACT We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was also reported to be highly upregulated in multiple types of human cancer. It was implied to play indispensable roles in cancer cell survival and indicated its involvement in the maintenance of tumor-initiating cells. We conducted a high-throughput screening of a compound library followed by structure-activity relationship studies, and successfully obtained a highly potent MELK inhibitor OTSSP167 with IC 50  of 0.41 nM. OTSSP167 inhibited the phosphorylation of PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which we identified as novel MELK substrates and are important for stem-cell characteristics and invasiveness. The compound suppressed mammosphere formation of breast cancer cells and exhibited significant t
Read more

Rapamycin increases oxidative stress response gene expression in adult stem cells

Image
Rapamycin increases oxidative stress response gene expression in adult stem cells Abstract Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescence  in vitro  and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment, including superoxide dismutase 1, glutathione reductase, and delta-aminolevulinate dehydratase. When we examined the expression of these genes in 55-week-old wild typ
Read more

Stress Response of Glioblastoma Cells Mediated by miR-17-5p Targeting PTEN and the Passenger Strand miR-17-3p Targeting MDM2

Stress Response of Glioblastoma Cells Mediated by miR-17-5p Targeting PTEN and the Passenger Strand miR-17-3p Targeting MDM2 ABSTRACT Tumor development not only destroys the homeostasis of local tissues but also the whole body, and thus the tumor cells have to face the body’s defense system, a shortage of nutrition and oxygen, and chemotherapeutic drug treatment. In response to these stresses, tumor cells often alter gene expression and microRNA levels to facilitate survival. We have demonstrated that glioblastoma cells deprived of nutrition or treated with chemotherapeutics drugs expressed increased levels of miR-17. Ectopic transfection of miR-17 prolonged glioblastoma cell survival when the cells were deprived with nutrition or treated with chemotherapeutic drugs. Expression of miR-17 also promoted cell motility, invasion, and tube-like structure formation. We found that these phenotypes were the results of miR-17 targeting PTEN. As a consequence, HIF1α and VEGF were up-regulated. E
Read more