BCL3 acts as a negative regulator of transcription from the human T-cell leukemia virus type 1 long terminal repeat through interactions with TORC3.

Abstract

By associating with cyclic AMP-responsive element-binding protein (CREB), the human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates transcription from the HTLV-1 long terminal repeat (LTR), which contains multiple cyclic AMP-responsive elements. The transducers of regulated CREB activity (TORCs) were a recently identified family of CREB co-activators that bind to CREB to enhance CRE-mediated transcription. TORC3, a TORC family protein, dramatically enhances Tax-mediated transcription from the LTR. In this study, we performed a yeast two-hybrid screen using the N-terminal region of TORC3 as bait and identified B-cell chronic lymphatic leukemia protein 3 (BCL3) as a protein interacting with TORC3. This interaction was confirmed by glutathione S-transferase pulldown assays and co-immunoprecipitation experiments with detection by Western blotting. The ankyrin repeat domain of BCL3 interacted with TORC3. By using a luciferase assay, we determined that BCL3 inhibited transcription from the HTLV-1 LTR in a manner dependent on TORC3. Knockdown of endogenous BCL3 using RNA interference enhanced transcriptional activation of CRE. Treatment with trichostatin A, a potent inhibitor of the transcriptional co-repressor HDAC, partially reversed the inhibitory effect of BCL3. These results suggest that BCL3 functions as a repressor of HTLV-1 LTR-mediated transcription through interactions with TORC3. In addition to stimulating transcription from the HTLV-1 LTR, Tax also enhances BCL3 expression; thus, transcription from the LTR is regulated by both positive and negative feedback mechanisms.

• Authors: Takayuki Hishiki, Takayuki Ohshima, Takeshi Ego, Kunitada Shimotohno
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 282 Issue 39 Pg. 28335-28343 (Sep 28 2007) ISSN: 0021-9258 [Print] United States
• PMID: 17644518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B-Cell Lymphoma 3 Protein
• BCL3 protein, human
• CREB1 protein, human
• CRTC3 protein, human
• Cyclic AMP Response Element-Binding Protein
• Enzyme Inhibitors
• Gene Products, tax
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Proto-Oncogene Proteins
• Repressor Proteins
• Transcription Factors
• trichostatin A

Topics

• B-Cell Lymphoma 3 Protein
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Enzyme Inhibitors (pharmacology)
• Gene Products, tax (metabolism)
• HeLa Cells
• Histone Deacetylase Inhibitors
• Human T-lymphotropic virus 1 (physiology)
• Humans
• Hydroxamic Acids (pharmacology)
• Protein Binding (physiology)
• Protein Structure, Tertiary (physiology)
• Proto-Oncogene Proteins (metabolism)
• RNA Interference
• Repressor Proteins (metabolism)
• Terminal Repeat Sequences (physiology)
• Transcription Factors (metabolism)
• Transcription, Genetic (drug effects, physiology)
• Transcriptional Activation (drug effects, physiology)