{"id":{"repo_id":"siu-theses","oai_identifier":"oai:opensiuc.lib.siu.edu:dissertations-1268"},"canonical_url":"https://search.dev.ndltd.org/etd/siu-theses/oai:opensiuc.lib.siu.edu:dissertations-1268","repository":{"repo_id":"siu-theses","name":"Southern Illinois University","base_url":"https://opensiuc.lib.siu.edu/do/oai/"},"display":{"title":"IDENTIFYING, CHARACTERIZING AND VERIFYING NOVEL C-MAF FUNCTIONS IN T CELL DEVELOPMENT AND APOPTOSIS","abstract":"T lymphocytes are necessary for an effective immune response; they protect us by destroying pathogens. Aside from their obvious importance in human health, the highly specialized and tightly controlled activities of T cells offer a unique test case for understanding cell regulation. This study is to investigate the mechanisms underlying c-Maf mediated control of developing and mature T cells. c-Maf, a basic leucine zipper transcription factor, is well known for its ability to promote T helper 2 (Th2) differentiation by direct transactivation of IL-4 following interaction with a consensus half MARE (Maf Response Element) site in the promoter. Although other c-Maf target genes are suggested by studies that demonstrate IL-4 independent changes occur in T cells that overexpress c-Maf, no specific genes have been identified yet. Studies presented here demonstrate that the function of c-Maf in T lineage cells can now be extended beyond transactivation of IL-4. Overexpression of c-Maf results in increased susceptibility of T cells to apoptosis induced by multiple stimuli, including growth factor withdrawal, dexamethasone, irradiation and T cell receptor (TCR) engagement. We also identified the mechanisms responsible for c-Maf regulation of apoptosis, which differ depending on the T cell lineage. In CD4 cells, c-Maf inhibits c-Myb binding to the Bcl-2 P2 promoter by interacting with c-Myb, which in turn disrupts Bcl-2 promoter activity. Downregulation of Bcl-2 expression limits CD4 cell survival following exposure to various stimuli. In CD8 cells, c-Maf transactivates Caspase 6 via binding to a consensus MARE site within the first intron. Upregulation of caspase 6 expression in c-Maf transgenic (Tg) cells provides increased substrate for caspase 6-dependent apoptosis pathways. In addition to influencing mature T cell survival, our studies show that c-Maf also regulates thymopoiesis. Largely independent of c-Myb and IL-4, overexpression of c-Maf influences thymocyte apoptosis, proliferation and emigration. Overall, c-Maf coordinates multiple processes including development and survival of T cells. Knowledge gained through these studies can be used to not only construct a more complete paradigm of c-Maf function in T cell immunity, but also evaluate c-Maf function as a predictive marker of autoimmune diseases.","abstract_html":"T lymphocytes are necessary for an effective immune response; they protect us by destroying pathogens. Aside from their obvious importance in human health, the highly specialized and tightly controlled activities of T cells offer a unique test case for understanding cell regulation. This study is to investigate the mechanisms underlying c-Maf mediated control of developing and mature T cells. c-Maf, a basic leucine zipper transcription factor, is well known for its ability to promote T helper 2 (Th2) differentiation by direct transactivation of IL-4 following interaction with a consensus half MARE (Maf Response Element) site in the promoter. Although other c-Maf target genes are suggested by studies that demonstrate IL-4 independent changes occur in T cells that overexpress c-Maf, no specific genes have been identified yet. Studies presented here demonstrate that the function of c-Maf in T lineage cells can now be extended beyond transactivation of IL-4. Overexpression of c-Maf results in increased susceptibility of T cells to apoptosis induced by multiple stimuli, including growth factor withdrawal, dexamethasone, irradiation and T cell receptor (TCR) engagement. We also identified the mechanisms responsible for c-Maf regulation of apoptosis, which differ depending on the T cell lineage. In CD4 cells, c-Maf inhibits c-Myb binding to the Bcl-2 P2 promoter by interacting with c-Myb, which in turn disrupts Bcl-2 promoter activity. Downregulation of Bcl-2 expression limits CD4 cell survival following exposure to various stimuli. In CD8 cells, c-Maf transactivates Caspase 6 via binding to a consensus MARE site within the first intron. Upregulation of caspase 6 expression in c-Maf transgenic (Tg) cells provides increased substrate for caspase 6-dependent apoptosis pathways. In addition to influencing mature T cell survival, our studies show that c-Maf also regulates thymopoiesis. Largely independent of c-Myb and IL-4, overexpression of c-Maf influences thymocyte apoptosis, proliferation and emigration. Overall, c-Maf coordinates multiple processes including development and survival of T cells. Knowledge gained through these studies can be used to not only construct a more complete paradigm of c-Maf function in T cell immunity, but also evaluate c-Maf function as a predictive marker of autoimmune diseases.","abstract_has_math":false,"creators":["Peng, Siying"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Campus Only Dissertation","degree_discipline":"Molecular Biology, Microbiology and Biochemistry","degree_department":null,"school":null,"contributors":["Pauza, Mary"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-01-01T08:00:00Z","date_published":"2008-01-01T08:00:00Z","updated_at":"2026-07-24T04:33:39Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://opensiuc.lib.siu.edu/dissertations/268","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Pauza, Mary"]},{"key":"dc:creator","label":"Author","values":["Peng, Siying"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular Biology, Microbiology and Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Campus Only Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://opensiuc.lib.siu.edu/dissertations/268"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["T lymphocytes are necessary for an effective immune response; they protect us by destroying pathogens. Aside from their obvious importance in human health, the highly specialized and tightly controlled activities of T cells offer a unique test case for understanding cell regulation. This study is to investigate the mechanisms underlying c-Maf mediated control of developing and mature T cells. c-Maf, a basic leucine zipper transcription factor, is well known for its ability to promote T helper 2 (Th2) differentiation by direct transactivation of IL-4 following interaction with a consensus half MARE (Maf Response Element) site in the promoter. Although other c-Maf target genes are suggested by studies that demonstrate IL-4 independent changes occur in T cells that overexpress c-Maf, no specific genes have been identified yet. Studies presented here demonstrate that the function of c-Maf in T lineage cells can now be extended beyond transactivation of IL-4. Overexpression of c-Maf results in increased susceptibility of T cells to apoptosis induced by multiple stimuli, including growth factor withdrawal, dexamethasone, irradiation and T cell receptor (TCR) engagement. We also identified the mechanisms responsible for c-Maf regulation of apoptosis, which differ depending on the T cell lineage. In CD4 cells, c-Maf inhibits c-Myb binding to the Bcl-2 P2 promoter by interacting with c-Myb, which in turn disrupts Bcl-2 promoter activity. Downregulation of Bcl-2 expression limits CD4 cell survival following exposure to various stimuli. In CD8 cells, c-Maf transactivates Caspase 6 via binding to a consensus MARE site within the first intron. Upregulation of caspase 6 expression in c-Maf transgenic (Tg) cells provides increased substrate for caspase 6-dependent apoptosis pathways. In addition to influencing mature T cell survival, our studies show that c-Maf also regulates thymopoiesis. Largely independent of c-Myb and IL-4, overexpression of c-Maf influences thymocyte apoptosis, proliferation and emigration. Overall, c-Maf coordinates multiple processes including development and survival of T cells. Knowledge gained through these studies can be used to not only construct a more complete paradigm of c-Maf function in T cell immunity, but also evaluate c-Maf function as a predictive marker of autoimmune diseases."]},{"key":"dc:title","label":"Title","values":["IDENTIFYING, CHARACTERIZING AND VERIFYING NOVEL C-MAF FUNCTIONS IN T CELL DEVELOPMENT AND APOPTOSIS"]}]}],"canonical_facts":{"dc:contributor":["Pauza, Mary"],"dc:creator":["Peng, Siying"],"dc:description.abstract":["T lymphocytes are necessary for an effective immune response; they protect us by destroying pathogens. Aside from their obvious importance in human health, the highly specialized and tightly controlled activities of T cells offer a unique test case for understanding cell regulation. This study is to investigate the mechanisms underlying c-Maf mediated control of developing and mature T cells. c-Maf, a basic leucine zipper transcription factor, is well known for its ability to promote T helper 2 (Th2) differentiation by direct transactivation of IL-4 following interaction with a consensus half MARE (Maf Response Element) site in the promoter. Although other c-Maf target genes are suggested by studies that demonstrate IL-4 independent changes occur in T cells that overexpress c-Maf, no specific genes have been identified yet. Studies presented here demonstrate that the function of c-Maf in T lineage cells can now be extended beyond transactivation of IL-4. Overexpression of c-Maf results in increased susceptibility of T cells to apoptosis induced by multiple stimuli, including growth factor withdrawal, dexamethasone, irradiation and T cell receptor (TCR) engagement. We also identified the mechanisms responsible for c-Maf regulation of apoptosis, which differ depending on the T cell lineage. In CD4 cells, c-Maf inhibits c-Myb binding to the Bcl-2 P2 promoter by interacting with c-Myb, which in turn disrupts Bcl-2 promoter activity. Downregulation of Bcl-2 expression limits CD4 cell survival following exposure to various stimuli. In CD8 cells, c-Maf transactivates Caspase 6 via binding to a consensus MARE site within the first intron. Upregulation of caspase 6 expression in c-Maf transgenic (Tg) cells provides increased substrate for caspase 6-dependent apoptosis pathways. In addition to influencing mature T cell survival, our studies show that c-Maf also regulates thymopoiesis. Largely independent of c-Myb and IL-4, overexpression of c-Maf influences thymocyte apoptosis, proliferation and emigration. Overall, c-Maf coordinates multiple processes including development and survival of T cells. Knowledge gained through these studies can be used to not only construct a more complete paradigm of c-Maf function in T cell immunity, but also evaluate c-Maf function as a predictive marker of autoimmune diseases."],"dc:identifier":["https://opensiuc.lib.siu.edu/dissertations/268"],"dc:title":["IDENTIFYING, CHARACTERIZING AND VERIFYING NOVEL C-MAF FUNCTIONS IN T CELL DEVELOPMENT AND APOPTOSIS"],"thesis:degree_discipline":["Molecular Biology, Microbiology and Biochemistry"],"thesis:degree_level":["Campus Only Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T04:33:39Z"}