Gankyrin is an oncoprotein overexpressed in hepatocarcinoma cells that binds to the cell-cycle regulator CDK4 and the S6b ATPase subunit of the regulatory component of the proteasome. It belongs to the family of ankyrin-repeat proteins that appear to mediate protein-protein interactions in diverse biochemical processes. Gankyrin has been crystallized from polyethylene glycol solutions and diffraction data have been obtained from these crystals that extend to 2.1 A spacing.
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Structural modification of the propyl linker of cjoc42 in combination with sulfonate ester and triazole replacements for enhanced gankyrin binding and anti-proliferative activity.
Bioorg Med Chem
August 2024
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, USA. Electronic address:
Liver cancer is a complex disease that involves various oncoproteins and the inactivation of tumor suppressor proteins (TSPs). Gankyrin is one such oncoprotein, first identified in human hepatocellular carcinoma, that is known to inactivate multiple TSPs, leading to proliferation and metastasis of tumor cells. Despite this, there has been limited development of small molecule gankyrin binders for the treatment of liver cancer.
View Article and Find Full Text PDFGankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.
Sci Rep
December 2023
Department of Breast and Thyroid Surgery, The Second Affiliated Hospital, Hainan Medical University, Haikou, 570311, China.
Gankyrin is found in high levels in triple-negative breast cancer (TNBC) and has been established to form a complex with the E3 ubiquitin ligase MDM2 and p53, resulting in the degradation of p53 in hepatocarcinoma cells. Therefore, this study sought to determine whether gankyrin could inhibit ferroptosis through this mechanism in TNBC cells. The expression of gankyrin was investigated in relation to the prognosis of TNBC using bioinformatics.
View Article and Find Full Text PDFextract reduces gastric cancerous properties through inhibition of gankyrin in cellular milieu produced by and Epstein Barr virus.
J Biomol Struct Dyn
November 2024
Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, India.
and Epstein Barr virus (EBV) are group1 carcinogens and their role in Gastric cancer (GC) is well established. Previously we have shown that and EBV appears to support aggressive gastric oncogenesis through the upregulation of oncoprotein Gankyrin. Natural plant active molecules have the potential to interrupt oncogenesis.
View Article and Find Full Text PDFSecond Generation Small Molecule Inhibitors of Gankyrin for the Treatment of Pediatric Liver Cancer.
Cancers (Basel)
June 2022
Division of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Background: Gankyrin, a member of the 26S proteasome, is an overexpressed oncoprotein in hepatoblastoma (HBL) and hepatocellular carcinoma (HCC). Cjoc42 was the first small molecule inhibitor of Gankyrin developed; however, the IC50 values of >50 μM made them unattractive for clinical use. Second-generation inhibitors demonstrate a stronger affinity toward Gankyrin and increased cytotoxicity.
View Article and Find Full Text PDFSmall-Molecule Gankyrin Inhibition as a Therapeutic Strategy for Breast and Lung Cancer.
J Med Chem
July 2022
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York 11439, United States.
Gankyrin is an oncoprotein responsible for the development of numerous cancer types. It regulates the expression levels of multiple tumor suppressor proteins (TSPs) in liver cancer; however, gankyrin's regulation of these TSPs in breast and lung cancers has not been thoroughly investigated. Additionally, no small-molecule gankyrin inhibitor has been developed which demonstrates potent anti-proliferative activity against gankyrin overexpressing breast and lung cancers.
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