The role of USP27X ablation in reducing cyclin D1
One of the current projects in the Atanassov lab is focused on validating Ubiquitin Specific Protease 27X (USP27X) as a drug target in breast and lung cancers. Higher expression of USP27X significantly correlates with poor survival in several cancers, including breast and lung cancer.
Importantly, our work and work from others demonstrated that USP27X ablation severely reduces the tumorigenicity of several cancer cell line xenograft models while its overexpression stimulates tumor cell growth.
Our recent studies demonstrated that functions of this DUB are critical for maintaining the steady-state protein levels of Cyclin D1, whose expression is crucial for cancer cell growth and resistance to therapy. Ablation of USP27X severely reduces the Cyclin D1 in cancer cells, inhibits tumor growth, and sensitizes cancer cells to therapy.
To fully understand the in vivo functions of USP27X in Cyclin D1 stability and its impact on tumor development, we created a new mouse line carrying a conditional USP27X allele and introduced this allele into the well-established and clinically relevant mouse cancer models.
Using these mice and several USP27X-engineered cell lines, we aim to validate USP27X as a critical therapeutic target in breast cancer through CCND1 degradation.
The role of USP51 in ovarian cancer
Another project in the laboratory investigates the role of USP51, a DUB that regulates histones H2A and H2B ubiquitination in ovarian cancer. The expression levels of this DUB are substantially reduced in platinum-resistant ovarian cancer.
Our studies revealed that USP51 regulates the activity of the epigenetic repressor polycomb complex in ovarian cancer cells, and USP51 ablation further sensitizes these cells to EZH2 inhibitors.
Connect with the Atanassov Lab
Email: Boyko.Atanassov@RoswellPark.org
Office Phone: 716-845-3037
Lab Location: Center for Genetics & Pharmacology (CGP) L4-321
Department of Pharmacology & Therapeutics
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263