| Structural highlights
Disease
BCL6_HUMAN Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
Function
BCL6_HUMAN Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.[1] [2]
Publication Abstract from PubMed
Developing cancer therapies that induce robust death of the malignant cell is critical to prevent relapse. Highly effective strategies, such as immunotherapy, exemplify this observation. Here we provide the structural and molecular underpinnings for an approach that leverages chemical induced proximity to produce specific cell killing of diffuse large B cell lymphoma, the most common non-Hodgkin's lymphoma. We develop KAT-TCIPs (lysine acetyltransferase transcriptional/epigenetic chemical inducers of proximity) that redirect p300 and CBP to activate programmed cell death genes normally repressed by the oncogenic driver, BCL6. Acute treatment rapidly reprograms the epigenome to initiate apoptosis and repress c-MYC. The crystal structure of the chemically induced p300-BCL6 complex reveals how chance interactions between the two proteins can be systematically exploited to produce the exquisite potency and selectivity of KAT-TCIPs. Thus, the malignant function of an oncogenic driver can be co-opted to activate robust cell death, with implications for precision epigenetic therapies.
A Bivalent Molecular Glue Linking Lysine Acetyltransferases to Oncogene-induced Cell Death.,Nix MN, Gourisankar S, Sarott RC, Dwyer BG, Nettles SA, Martinez MM, Abuzaid H, Yang H, Wang Y, Simanauskaite JM, Romero BA, Jones HM, Krokhotin A, Lowensohn TN, Chen L, Low C, Davis MM, Fernandez D, Zhang T, Green MR, Hinshaw SM, Gray NS, Crabtree GR bioRxiv [Preprint]. 2025 Mar 17:2025.03.14.643404. doi: , 10.1101/2025.03.14.643404. PMID:40166243[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Niu H, Ye BH, Dalla-Favera R. Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 1998 Jul 1;12(13):1953-61. PMID:9649500
- ↑ Ghetu AF, Corcoran CM, Cerchietti L, Bardwell VJ, Melnick A, Prive GG. Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol Cell. 2008 Feb 15;29(3):384-91. PMID:18280243 doi:10.1016/j.molcel.2007.12.026
- ↑ Nix MN, Gourisankar S, Sarott RC, Dwyer BG, Nettles SA, Martinez MM, Abuzaid H, Yang H, Wang Y, Simanauskaite JM, Romero BA, Jones HM, Krokhotin A, Lowensohn TN, Chen L, Low C, Davis MM, Fernandez D, Zhang T, Green MR, Hinshaw SM, Gray NS, Crabtree GR. A Bivalent Molecular Glue Linking Lysine Acetyltransferases to Oncogene-induced Cell Death. bioRxiv [Preprint]. 2025 Mar 17:2025.03.14.643404. PMID:40166243 doi:10.1101/2025.03.14.643404
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