Human delta Np73 regulates a dominant negative feedback loop for TAp73 and p53

Area of Science:

• Molecular Biology
• Cancer Research
• Genetics

Background:

• Tumor suppressor p53 inactivation is common in cancer.
• p53 regulates cell cycle arrest and apoptosis in response to genotoxic stress.
• p73 protein shares structural and functional similarities with p53.

Purpose of the Study:

• To clone and characterize human Delta Np73 isoforms.
• To investigate the regulation of Delta Np73 by p53.
• To explore the role of Delta Np73 in carcinogenesis.

Main Methods:

• Cloning and characterization of human Delta Np73.
• Analysis of Delta Np73 regulation by p53 and p73 isoforms.
• Investigation of Delta Np73's effect on p53 and TAp73 function.

Main Results:

• Human Delta Np73 lacks the transactivation domain and is regulated by a separate promoter.
• Delta Np73 inhibits the transactivation activity and apoptosis-inducing functions of p53 and TAp73.
• Delta Np73 expression is upregulated by p53 and TA isoforms, forming a feedback loop.

Conclusions:

• Delta Np73 acts as a negative regulator of p53 and TAp73.
• The feedback loop involving Delta Np73 finely tunes p53 and TAp73 activity.
• Increased Delta Np73 expression, by inactivating p53, may play a role in tumorogenesis.