Détail du document
Identifiant
oai:pubmedcentral.nih.gov:1105...
Auteur
Huang, Qi-xuan Fan, Da-meng Zheng, Zao-zao Ran, Ting Bai, Ao Xiao, Rong-quan Hu, Guo-sheng Liu, WenLangue
enEditeur
American Chemical Society
Catégorie
ACS AuthorChoice
Année
2024
Date de référencement
10/06/2024
Mots clés
oncogene tat-piet expression brd4 breast cancerRésumé
[Image: see text] BRD4 is associated with a variety of human diseases, including breast cancer.
The crucial roles of amino-terminal bromodomains (BDs) of BRD4 in binding with acetylated histones to regulate oncogene expression make them promising drug targets.
However, adverse events impede the development of the BD inhibitors.
BRD4 adopts an extraterminal (ET) domain, which recruits proteins to drive oncogene expression.
We discovered a peptide inhibitor PiET targeting the ET domain to disrupt BRD4/JMJD6 interaction, a protein complex critical in oncogene expression and breast cancer.
The cell-permeable form of PiET, TAT-PiET, and PROTAC-modified TAT-PiET, TAT-PiET-PROTAC, potently inhibits the expression of BRD4/JMJD6 target genes and breast cancer cell growth.
Combination therapy with TAT-PiET/TAT-PiET-PROTAC and JQ1, iJMJD6, or Fulvestrant exhibits synergistic effects.
TAT-PiET or TAT-PiET-PROTAC treatment overcomes endocrine therapy resistance in ERα-positive breast cancer cells.
Taken together, we demonstrated that targeting the ET domain is effective in suppressing breast cancer, providing a therapeutic avenue in the clinic.
Huang, Qi-xuan,Fan, Da-meng,Zheng, Zao-zao,Ran, Ting,Bai, Ao,Xiao, Rong-quan,Hu, Guo-sheng,Liu, Wen, 2024, Peptide Inhibitor Targeting the Extraterminal Domain in BRD4 Potently Suppresses Breast Cancer Both In Vitro and In Vivo, American Chemical Society
Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex
heterogeneity projection-specific
