INTERACTION BETWEEN HTLV-1 BASIC LEUCINE ZIPPER FACTOR (HBZ) AND HOST CELL PROTEINS PROMOTES CELLULAR TRANSFORMATION
Human T-cell Leukemia Virus Type 1 (HTLV-1) is a complex retrovirus which preferentially infects CD4+ T-cells. Endemic to Japan, regions of South America, Africa, and the Caribbean, HTLV-1 is transmitted through breastfeeding, sexual contact, and contact with infected blood or blood products. In 5% of cases, HTLV-1 infection leads to Adult T-cell Leukemia (ATL) after a 40 to 60 year period of low viral activity. Diagnosis of ATL is equivalent to a death sentence as currently available treatments only serve to extend the life of patients by a few months. HTLV-1 encodes unique regulatory and accessory proteins which are important for viral replication as well as modulating host cell activities. One of these proteins includes the HTLV-1 basic leucine zipper factor (HBZ). Clinical research reveals that HBZ is the only viral protein consistently expressed in patients with ATL, and in vitro transformation assays support that HBZ is important for cellular transformation. The exact mechanisms by which HBZ promotes cellular transformation are not known; therefore, understanding the molecular biology of HBZ and other proteins is important for developing effective treatments for ATL. HBZ is a nuclear protein that has been shown to interact with cellular transcription factors in the CREB/ATF and AP-1 families, as well as with coactivators including p300/CBP. These interactions regulate or deregulate expression of host cell and proviral genes. One focus in our laboratory is to identify and characterize novel interactions between HBZ and cellular proteins. HBZ interactome studies performed in our laboratory reveal that HBZ interacts with the small Maf family of basic leucine zipper (bZIP) transcriptional regulators. Leucine zipper dimerization between small Mafs and other compatible bZIP proteins allows them to be recruited to Maf Responsive Elements (MAREs) on the genomic DNA as transcriptionally repressive homodimers, or as transcriptionally active heterodimers. We found that interaction between HBZ and small Mafs occurs directly through a dimerization of each protein’s leucine zipper using in vitro GST pulldown assays.
Amanda Rushing served as the co-mentor for this thesis project.
Sanders, Stephanie. (April 2016). INTERACTION BETWEEN HTLV-1 BASIC LEUCINE ZIPPER FACTOR (HBZ) AND HOST CELL PROTEINS PROMOTES CELLULAR TRANSFORMATION (Honors Thesis, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/5221.)
Sanders, Stephanie. INTERACTION BETWEEN HTLV-1 BASIC LEUCINE ZIPPER FACTOR (HBZ) AND HOST CELL PROTEINS PROMOTES CELLULAR TRANSFORMATION. Honors Thesis. East Carolina University, April 2016. The Scholarship. http://hdl.handle.net/10342/5221. August 21, 2019.
Sanders, Stephanie, “INTERACTION BETWEEN HTLV-1 BASIC LEUCINE ZIPPER FACTOR (HBZ) AND HOST CELL PROTEINS PROMOTES CELLULAR TRANSFORMATION” (Honors Thesis., East Carolina University, April 2016).
Sanders, Stephanie. INTERACTION BETWEEN HTLV-1 BASIC LEUCINE ZIPPER FACTOR (HBZ) AND HOST CELL PROTEINS PROMOTES CELLULAR TRANSFORMATION [Honors Thesis]. Greenville, NC: East Carolina University; April 2016.