TRAF-3 mRNA splice-deletion variants encode isoforms that induce NF-kappaB activation.

Area of Science:

• Immunology
• Molecular Biology
• Cell Signaling

Background:

• Tumor necrosis factor receptor-associated factor 3 (TRAF-3) is crucial for T-B cell collaboration.
• Full-length TRAF-3 lacks signaling function in NF-kappaB activation assays.
• The TRAF-3 gene produces splice-deletion variants with altered zinc finger domains and unknown functions.

Purpose of the Study:

• To investigate the signaling capacity of TRAF-3 splice-deletion variants.
• To determine if these variants can transmit receptor signals to the nucleus.
• To analyze the expression and function of eight TRAF-3 splice-deletion variants.

Main Methods:

• Cloning of five additional TRAF-3 splice-variant isoforms.
• Analysis of expression of TRAF-3 splice variants in B and T cell lines.
• Functional analysis of TRAF-3 variants in NF-kappaB activation assays using 293 T cells.

Main Results:

• TRAF-3 delta130 mRNA and TRAF-3 delta221 protein are expressed in B and T cells.
• Seven TRAF-3 splice-deletion variants, including delta130, induced significant NF-kappaB activation (80-500 fold).
• Full-length TRAF-3 augmented the activity of the seven activating variants (1.4-5 fold), while delta221 was inactive.

Conclusions:

• Alterations in zinc finger domains enable TRAF-3 splice-deletion variants to activate NF-kappaB signaling.
• TRAF-3 splice variants play a role in transmitting signals to the nucleus.
• Full-length TRAF-3 modulates the signaling capacity of its splice variants.