Bcl6

Overview

Bcl6 (B-cell lymphoma 6) is a transcription factor that plays a critical role in the regulation of gene expression in B cells. It is encoded by the BCL6 gene located on chromosome 3 in humans. Bcl6 is essential for the formation of germinal centers and is involved in the process of somatic hypermutation and class switch recombination in B cells.

Structure

Bcl6 is a zinc finger transcription factor, characterized by its BTB/POZ domain at the N-terminus and six C2H2 zinc finger motifs at the C-terminus. The BTB/POZ domain is involved in protein-protein interactions, while the zinc finger motifs are responsible for DNA binding.

Function

Bcl6 functions primarily as a transcriptional repressor. It binds to specific DNA sequences and recruits corepressor complexes, such as SMRT and NCoR, to inhibit the transcription of target genes. Bcl6 is crucial for the development and function of germinal center B cells, where it regulates genes involved in cell cycle, apoptosis, and DNA repair.

Role in Germinal Centers

In germinal centers, Bcl6 is required for the proliferation and survival of B cells. It suppresses the expression of p53, CDKN1A (p21), and other pro-apoptotic genes, allowing B cells to undergo rapid division and affinity maturation. Bcl6 also represses genes involved in plasma cell differentiation, maintaining the B cell phenotype.

Role in T Cells

Bcl6 is also expressed in certain subsets of T cells, such as T follicular helper cells (Tfh). In Tfh cells, Bcl6 is necessary for their differentiation and function, promoting the expression of CXCR5 and other Tfh-specific genes.

Clinical Significance

Bcl6 is implicated in the pathogenesis of several lymphomas, particularly diffuse large B-cell lymphoma (DLBCL). In DLBCL, Bcl6 is often overexpressed due to chromosomal translocations or mutations that disrupt its regulation. This overexpression contributes to the malignant phenotype by inhibiting apoptosis and promoting cell proliferation.

Therapeutic Target

Given its role in lymphomas, Bcl6 is a potential target for therapeutic intervention. Small molecule inhibitors and peptidomimetics that disrupt Bcl6 function are being investigated as treatments for Bcl6-positive lymphomas.

Research Directions

Ongoing research is focused on understanding the full spectrum of Bcl6 target genes and its interactions with other transcription factors and corepressors. There is also interest in the role of Bcl6 in other immune cells and its potential involvement in autoimmune diseases.

See Also

• Transcription factor
• Germinal center
• Diffuse large B-cell lymphoma
• Zinc finger

This article is a stub related to proteins. You can help WikiMD by expanding it!