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Abstract
A region on chromosome 21, the Down Syndrome critical region (DSCR), is associated with major defects found in Down Syndrome, such as craniofacial malformations. DYRK1A is a gene found on chromosome 21 within the DSCR that encodes an enzyme, dual specificity tyrosine-phosphorylation-regulated kinase 1A. DYRK1A is known to phosphorylate many substrate proteins and is thought to be involved in tumor suppression, neurological development, cell cycle regulation, and aging. Recently, the Litovchick lab and others reported that DYRK1A also plays a role in the double-strand break repair of DNA, which could lead to mutations and tumorigenesis, if deregulated.
The Litovchick lab is currently investigating novel interactions of DYRK1A, and their implications for cancer. One of these proteins, DCAF7, is already a well-known DYRK1A interacting partner. Another less characterized protein is LZTS2, also known as LAPSER1 or leucine-zipper tumor suppressor 2. LZTS2 is found to be deleted in many human tumors and is known to bind a signaling intermediate SIPA1L1.2 Our preliminary data show that LZTS2 may promote DYRK1A phosphorylation, thereby regulating DYRK1A kinase activity. We suspect that SIPA1L1 may be involved in this interaction and, as this complex is known to be involved in the WNT pathway that plays a role in both cancer and orofacial formation,
To test this hypothesis, we started characterization of the DYRK1A-LZTS2 interaction using ectopic expressions of the full-length LZTS2 and DYRK1A as well as their fragments expressed in human T98G cells. We will further perform experiments investigating the physical binding and functional interactions between DCAF7, SIPA1L1, and the DYRK1A-LZTS2 complex.
Publication Date
2023
Subject Major(s)
Cancer Research
Disciplines
Genetic Processes | Hematology | Medical Cell Biology | Medical Molecular Biology | Oncology
Current Academic Year
Junior
Faculty Advisor/Mentor
Dr. Larisa Litovchick, MD/PhD
Rights
© The Author(s)
Included in
Genetic Processes Commons, Hematology Commons, Medical Cell Biology Commons, Medical Molecular Biology Commons, Oncology Commons