Theses and Dissertations

ORCID

https://orcid.org/0009-0000-2839-0176

Advisor

Collins, Galen

Committee Member

Hoffmann, Federico

Committee Member

Krishnan, Natraj

Date of Degree

5-15-2026

Original embargo terms

Visible MSU Only 1 year

Document Type

Graduate Thesis - Campus Access Only

Major

Agricultural Life Sciences (Biochemistry)

Degree Name

Master of Science (M.S.)

College

College of Agriculture and Life Sciences

Department

Department of Biochemistry, Nutrition and Health Promotion

Abstract

DNA-damage inducible 1 homolog 2 is a ubiquitin-dependent retroviral-like endoprotease that can also shuttle ubiquitin conjugates to the proteasome for degradation. Inhibiting DDI2 increases major histocompatibility complex class I (MHC-I) antigen presentation and triggers the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. However, both increased MHC-I antigen presentation and UPR signaling diminish over time. Therefore, we hypothesized that the genetic loss of DDI2 induces transcriptional adaptation, whereby functionally related genes are upregulated to compensate for DDI2 loss. We examined the expression of human shuttling factors and retroviral-like proteases in human cancer cell lines with genetically inactivated DDI2. In this study, we identified six potential candidate genes that may compensate. Additionally, publicly available gene expression data from the cancer dependency map (DepMap) was used to identify novel genes most strongly associated with DDI2 expression, generating new potential compensatory genes and related signaling pathways.

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