A novel aryl hydrocarbon receptor nuclear translocator (ARNT)-interacting peptide (Ainpl) was characterized from human liver cDNA library using phage display. Ainpl suppresses hypoxia inducible factor-1a (HIF-1α) signaling pathway through an ARNTdependent manner. HIF-1α is known to be overexpressed in more than 90% of solid tumors, and the inhibition of HIF-1α is proved as an effective approach to suppress tumor growth. ARNT, as the obligatory heterodimeric partner of HIF-1α for downstream gene activation, was used as a bait to screen for Ainpl. Ainpl specifically interacts with the helix-loop-helix (HLH) subdomain of ARNT, but not with HIF-1α. GFP-Ainpl is localized in both cytoplasm and nucleus, and suppresses HIF-1α signaling by two mechanisms: (1) cytoplasmic GFP-Ainp 1 retains ARNT in the cell cytoplasm and (2) nuclear GFP-Ainpl inhibits HIF-1α/ARNT heterodimerization. The suppression of Ainpl on HIF-1α signaling was reversed by introducing ARNT into the cells using transient transfection. We further utilized HIV TAT protein transduction domain to deliver 6His-TAT-Ainpl into three different cancer cell lines (Hep3B, HeLa, MCF-7), and found that 6His-TAT-Ainpl co-localizes with ARNT in the cell nucleus. 6His-TATAinpl can be detected inside the cells after 30 min of transduction, and can reach the maximum level at 2 h. 6His-TAT-Ainp 1 remained detectable in the cells up to 96 h and had a half life of 24 h after transduction. In addition, 6His-TAT-Ainp 1 suppresses HIF-1α downstream genes at both message and protein levels in a dose-dependent manner. Taken together, molecules that target the HIF-1α and ARNT interface can be developed as viable drugs to suppress HIF-1α signaling.
","abstract_html":"<p>A novel aryl hydrocarbon receptor nuclear translocator (ARNT)-interacting peptide (Ainpl) was characterized from human liver cDNA library using phage display. Ainpl suppresses hypoxia inducible factor-1a (HIF-1α) signaling pathway through an ARNTdependent manner. HIF-1α is known to be overexpressed in more than 90% of solid tumors, and the inhibition of HIF-1α is proved as an effective approach to suppress tumor growth. ARNT, as the obligatory heterodimeric partner of HIF-1α for downstream gene activation, was used as a bait to screen for Ainpl. Ainpl specifically interacts with the helix-loop-helix (HLH) subdomain of ARNT, but not with HIF-1α. GFP-Ainpl is localized in both cytoplasm and nucleus, and suppresses HIF-1α signaling by two mechanisms: (1) cytoplasmic GFP-Ainp 1 retains ARNT in the cell cytoplasm and (2) nuclear GFP-Ainpl inhibits HIF-1α/ARNT heterodimerization. The suppression of Ainpl on HIF-1α signaling was reversed by introducing ARNT into the cells using transient transfection. We further utilized HIV TAT protein transduction domain to deliver 6His-TAT-Ainpl into three different cancer cell lines (Hep3B, HeLa, MCF-7), and found that 6His-TAT-Ainpl co-localizes with ARNT in the cell nucleus. 6His-TATAinpl can be detected inside the cells after 30 min of transduction, and can reach the maximum level at 2 h. 6His-TAT-Ainp 1 remained detectable in the cells up to 96 h and had a half life of 24 h after transduction. In addition, 6His-TAT-Ainp 1 suppresses HIF-1α downstream genes at both message and protein levels in a dose-dependent manner. Taken together, molecules that target the HIF-1α and ARNT interface can be developed as viable drugs to suppress HIF-1α signaling.</p>","abstract_has_math":false,"creators":["Wang, Yu"],"institution":null,"degree_name":"Doctor of Philosophy (Ph.D.)","degree_level":"Dissertation - Pacific Access Restricted","degree_discipline":"Pharmaceutical and Chemical Sciences","degree_department":null,"school":null,"contributors":["William K. Chan"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-01-01T08:00:00Z","date_published":"2013-01-01T08:00:00Z","updated_at":"2026-07-24T05:36:00Z","subjects":["Molecular biology","Toxicology","Surgery","Pharmacology","Biological sciences","Health and environmental sciences","Aryl hydrocarbon receptor","Hypoxia inducible factor","Nuclear translocators","Phage displays","Chemicals and Drugs","Chemistry","Medical Pharmacology","Medicinal-Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutical Preparations","Pharmacy and Pharmaceutical Sciences","Physical Sciences and Mathematics"],"languages":[],"rights":[],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9781303533938"],"render_values":[{"text":"9781303533938","href":null,"code":true}]}]},"links":{"outbound_url":"https://scholarlycommons.pacific.edu/uop_etds/151","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["William K. Chan"]},{"key":"dc:creator","label":"Author","values":["Wang, Yu"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-06-29T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutical and Chemical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation - Pacific Access Restricted"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (Ph.D.)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Molecular biology","Toxicology","Surgery","Pharmacology","Biological sciences","Health and environmental sciences","Aryl hydrocarbon receptor","Hypoxia inducible factor","Nuclear translocators","Phage displays","Chemicals and Drugs","Chemistry","Medical Pharmacology","Medicinal-Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutical Preparations","Pharmacy and Pharmaceutical Sciences","Physical Sciences and Mathematics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9781303533938","https://scholarlycommons.pacific.edu/uop_etds/151"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A novel aryl hydrocarbon receptor nuclear translocator (ARNT)-interacting peptide (Ainpl) was characterized from human liver cDNA library using phage display. Ainpl suppresses hypoxia inducible factor-1a (HIF-1α) signaling pathway through an ARNTdependent manner. HIF-1α is known to be overexpressed in more than 90% of solid tumors, and the inhibition of HIF-1α is proved as an effective approach to suppress tumor growth. ARNT, as the obligatory heterodimeric partner of HIF-1α for downstream gene activation, was used as a bait to screen for Ainpl. Ainpl specifically interacts with the helix-loop-helix (HLH) subdomain of ARNT, but not with HIF-1α. GFP-Ainpl is localized in both cytoplasm and nucleus, and suppresses HIF-1α signaling by two mechanisms: (1) cytoplasmic GFP-Ainp 1 retains ARNT in the cell cytoplasm and (2) nuclear GFP-Ainpl inhibits HIF-1α/ARNT heterodimerization. The suppression of Ainpl on HIF-1α signaling was reversed by introducing ARNT into the cells using transient transfection. We further utilized HIV TAT protein transduction domain to deliver 6His-TAT-Ainpl into three different cancer cell lines (Hep3B, HeLa, MCF-7), and found that 6His-TAT-Ainpl co-localizes with ARNT in the cell nucleus. 6His-TATAinpl can be detected inside the cells after 30 min of transduction, and can reach the maximum level at 2 h. 6His-TAT-Ainp 1 remained detectable in the cells up to 96 h and had a half life of 24 h after transduction. In addition, 6His-TAT-Ainp 1 suppresses HIF-1α downstream genes at both message and protein levels in a dose-dependent manner. Taken together, molecules that target the HIF-1α and ARNT interface can be developed as viable drugs to suppress HIF-1α signaling.
"]},{"key":"dc:source","label":"Dc Source","values":["184"]},{"key":"dc:title","label":"Title","values":["Mechanistic study of aryl hydrocarbon receptor nuclear translocator (ARNT)-mediated signaling"]}]}],"canonical_facts":{"dc:contributor":["William K. Chan"],"dc:creator":["Wang, Yu"],"dc:date.available":["2018-06-29T07:00:00Z"],"dc:description.abstract":["A novel aryl hydrocarbon receptor nuclear translocator (ARNT)-interacting peptide (Ainpl) was characterized from human liver cDNA library using phage display. Ainpl suppresses hypoxia inducible factor-1a (HIF-1α) signaling pathway through an ARNTdependent manner. HIF-1α is known to be overexpressed in more than 90% of solid tumors, and the inhibition of HIF-1α is proved as an effective approach to suppress tumor growth. ARNT, as the obligatory heterodimeric partner of HIF-1α for downstream gene activation, was used as a bait to screen for Ainpl. Ainpl specifically interacts with the helix-loop-helix (HLH) subdomain of ARNT, but not with HIF-1α. GFP-Ainpl is localized in both cytoplasm and nucleus, and suppresses HIF-1α signaling by two mechanisms: (1) cytoplasmic GFP-Ainp 1 retains ARNT in the cell cytoplasm and (2) nuclear GFP-Ainpl inhibits HIF-1α/ARNT heterodimerization. The suppression of Ainpl on HIF-1α signaling was reversed by introducing ARNT into the cells using transient transfection. We further utilized HIV TAT protein transduction domain to deliver 6His-TAT-Ainpl into three different cancer cell lines (Hep3B, HeLa, MCF-7), and found that 6His-TAT-Ainpl co-localizes with ARNT in the cell nucleus. 6His-TATAinpl can be detected inside the cells after 30 min of transduction, and can reach the maximum level at 2 h. 6His-TAT-Ainp 1 remained detectable in the cells up to 96 h and had a half life of 24 h after transduction. In addition, 6His-TAT-Ainp 1 suppresses HIF-1α downstream genes at both message and protein levels in a dose-dependent manner. Taken together, molecules that target the HIF-1α and ARNT interface can be developed as viable drugs to suppress HIF-1α signaling.
"],"dc:identifier":["9781303533938","https://scholarlycommons.pacific.edu/uop_etds/151"],"dc:rights":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:source":["184"],"dc:subject":["Molecular biology","Toxicology","Surgery","Pharmacology","Biological sciences","Health and environmental sciences","Aryl hydrocarbon receptor","Hypoxia inducible factor","Nuclear translocators","Phage displays","Chemicals and Drugs","Chemistry","Medical Pharmacology","Medicinal-Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutical Preparations","Pharmacy and Pharmaceutical Sciences","Physical Sciences and Mathematics"],"dc:title":["Mechanistic study of aryl hydrocarbon receptor nuclear translocator (ARNT)-mediated signaling"],"thesis:degree_discipline":["Pharmaceutical and Chemical Sciences"],"thesis:degree_level":["Dissertation - Pacific Access Restricted"],"thesis:degree_name":["Doctor of Philosophy (Ph.D.)"]},"updated_at":"2026-07-24T05:36:00Z"}