Exploring HIF-1 Alpha Destabilization Mechanisms in Cancer Cells

A small regulatory protein can be found not only in all humans, animals, plants and fungi, but in each and every eukaryotic cell. Following the discovery of these ubiquitous proteins in 1974, researchers aptly named them ubiquitin. Enzymes and/or ligases (enzymes that catalyze the formation of chemical bonds), allow ubiquitins to bind to substrate proteins. This process, known as ubiquitination, can initiate or prevent protein interactions, denote them for degradation and alter their activity and cellular location. Aberrant ubiquitination may play an important role in tumorigenesis. At the core of solid tumors, hypoxia-inducible factor 1α (HIF-1α) is induced (by hypoxia) and allows cancer cells to adapt to the lack of oxygen. The accumulation of HIF-1α can also transcribe a number of genes well-known to be involved in cancer. Therefore, HIF-1α is an attractive, albeit difficult-to-pinpoint, therapeutic target in cancer. Researchers—from Brown University and ​​Lifespan Cancer Institute—previously observed the stabilization of HIF-1α by the protein coding gene cyclin-dependent kinases CDK1. They further proposed that CDK4 may also be an HIF-1α stabilizer. However, the mechanism of HIF-1α’s regulation by CDK4 has yet to be fully elucidated. “Till now, development of therapies targeting HIF-1α remains hindered. Therefore, it is imperative to explore the mechanism of HIF-1α regulation in cancer cells and investigate new possibilities to therapeutically target HIF-1 signaling.” In 2021, the same team conducted a new study further investigating the molecular mechanisms of HIF-1α destabilization by CDK1 or CDK4/6 inhibitors in colorectal cancer. Their priority research paper was published as the cover of Oncotarget’s Volume 12, Issue 20, and entitled, “Identification of Smurf2 as a HIF-1α degrading E3 ubiquitin ligase.” Full blog - https://www.oncotarget.org/2021/09/30/new-study-protein-analysis-reveals-novel-role-of-enzyme-in-cancer/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28081 DOI - https://doi.org/10.18632/oncotarget.28081 Full text - https://www.oncotarget.com/article/28081/text/ Correspondence to - Wafik S. El-Deiry - wafik@brown.edu Keywords - Smurf2, CDK4/6 inhibition, HIF1alpha, hypoxia, cancer therapy About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957