CHARACTERIZING THE ROLE OF IRE1alpha IN EARLY STAGES OF UVB INDUCED NEOPLASTIC TRANSFORMATION
Open Access
- Author:
- Worrell, Stephen
- Area of Honors:
- Immunology and Infectious Disease
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Adam Bleier Glick, Thesis Supervisor
Pamela Hankey Giblin, Thesis Honors Advisor - Keywords:
- endoplasmic reticulum stress
skin cancer
UV radiation
Unfolded Protein Response - Abstract:
- The endoplasmic reticulum (ER) is a vital cell organelle with diverse function, however the primary function is protein production. This process is highly important and tightly regulated but, under different forms of environmental stimuli or disease, can become dysregulated. When proteins are produced improperly, they can accumulate to cause deleterious stress to the cell, termed ER stress. To mitigate this, cells initiate a process called the unfolded protein response (UPR). The three arms of the UPR are controlled by the proteins ATF-6, PERK, and IRE1alpha. This thesis will investigate the role of IRE1alpha in responding to acute and chronic UVB exposure. IRE1alpha is an ER membrane-spanning protein with two main effector functions in response to ER stress. First, upon UPR activation, IRE1alpha splices the transcription factor XBP-1 into the active form so it can translocate to the nucleus and regulate gene expression of many different proteins. Second, IRE1alpha will begin to degrade mRNA transcripts to decrease the protein levels to prevent more improper protein folding. These processes can significantly influence a cell’s response to environmental or disease induced stress. One important environmental stress Humans face every day is ultra-violet (UV) light from the sun. UV is a known inducer of ER stress and is the primary cause of skin cancer. Here, we worked to characterize how epidermal IRE1alpha plays a role in responding to acute and chronic UV-B exposure, using a congenital epidermal IRE1alpha knock-out mouse model.