Ubiquitin conjugating enzymes having transcriptional repressor activity

US5770720A · kind A · utility

Assignee

• Barnes-Jewish Hospital · US

Inventors

• Thomas F. Deuel · Cambridge, US
• Zhao Yi Wang · Bellevue, US
• Thomas Shenk · Princeton, US

Key dates

• Filing date: Aug 30, 1996
• Grant date: Jun 23, 1998
• Expiry date: Aug 30, 2016

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2760/16022
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A human ubiquitin conjugating enzyme, designated hUBC-9, its full amino acid sequence, and nucleic acid polymers which encode hUBC-9 are disclosed. In addition to having functional ubiquitin conjugating activity, this enzyme has transcriptional repressor activity which is independent of the conjugating activity. The conjugating activity of hUBC-9 enhances transcription through degradation of transcription suppressor proteins such as WT1, and possibly, of hUBC-9 itself. The repressor activity of hUBC-9 suppress gene transcription, probably by disrupting the transcriptional initiation complex through specific interactions with the DNA binding region of the TATA binding protein (TBP). In use, hUBC-9, yUBC-9 and other ubiquitin conjugating enzymes having repressor activity can be fused to proteins having a DNA binding domain, such as Gal4, or used in conjunction with reppressors such as Wilm's tumor suppressor gene product, WT1. Such enzymes and the nucleic acid polymers encoding them can be used for regulating transcription of a target gene in both pharmaceutical and non-pharmaceutical applications.