Interferon Regulatory Factor 8 (IRF8) Interacts with the B Cell Lymphoma 6 (BCL6) Corepressor BCOR

Yoon, Jeongheon; Feng, Xianxum; Kim, Yong Soo; Shin, Dong‐Mi; Hatzi, Katerina; Wang, Hongsheng; Morse, Herbert C.

doi:10.1074/jbc.m114.571182

Cited by 15 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in accord with concepts elaborated by Hodgkin and colleagues based on in vitro data, including recent elegant single-cell studies of short-term B cell cultures (Duffy et al, 2012). In this regard, mRNAs encoding several key transcription factors and co-factors related to GC, MBC and LLPC identity are differentially expressed in early and late GCBC, including Irf8, Egr1, Mef2b, Sh3bgrl2 (whose protein is an interacting partner with Irf8 (Yoon et al, 2014), and Zbtb20 (also known as Zfp288 ), which has been recently implicated in the development of LLPC (Chevrier and Corcoran, 2014; Nutt et al, 2015; Wang and Bhattacharya, 2014). …”

Section: Discussionmentioning

confidence: 99%

A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

et al. 2016

View full text Add to dashboard Cite

Summary There is little insight into or agreement about the signals that control differentiation of memory B cells (MBC) and long-lived plasma cells (LLPC). By performing BrdU pulse-labeling studies, we found that MBC formation preceded the formation of LLPC in an adoptive transfer immunization system, which allowed for a synchronized Ag-specific response with homogeneous Ag-receptor, yet at natural precursor frequencies. We confirmed observations in wild type (WT) mice and extended them with germinal center (GC) disruption experiments and variable region gene sequencing. We thus show that the GC response undergo a temporal switch in its output as it matures, revealing that the reaction engenders both MBC subsets with different immune effector function and, ultimately, LLPC at largely separate points in time. These data demonstrate the kinetics of the formation of the cells that provide stable humoral immunity and therefore have implications for autoimmunity, vaccine development, and for understanding long-term pathogen resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…A number of studies have shown that IRF8 is one of the key players in regulating B-cell development and functions 14 , 15 , 25 , 26 . However, IRF8's role in the development of B-cell malignancies remained elusive.…”

Section: Discussionmentioning

confidence: 99%

“…For lymphoid lineage, IRF8 was critical in controlling early stage B cell development as well as marginal zone and follicular B-cell development 13 , 14 . IRF8 positively regulated BCL6, a transcription factor critical for the development and function of germinal center B cells, through direct and indirect actions 15 . Mice deficient in Irf8 had impaired germinal center (GC) formation 16 .…”

Section: Introductionmentioning

confidence: 99%

Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma

Xu¹,

Jiang²,

Fang³

et al. 2015

J. Cancer

Self Cite

View full text Add to dashboard Cite

IRF8 is a transcription factor with a critical role in B lymphocyte development and functions. Its role in human diffuse large B-cell lymphoma (DLBCL), however, remained elusive. In this study, using shRNA-mediated knockdown of IRF8 expression, we found that the loss of IRF8 significantly reduced the proliferation of DLBCL cells (P<0.05). Mechanistically, decreasing the levels of IRF8 led to a suppression of the phosphorylation of p38 and ERK, molecules critical for B cell proliferation. Furthermore, using a xenograft lymphoma mouse model, we found that the loss of IRF8 significantly inhibited the growth of lymphomas in vivo (P<0.05). Immunohistochemical analysis of human DLBCL tissues revealed that the levels of IRF8 were significantly greater in non-germinal center B-cell-like (non-GCB) subtype than that in GCB subtype (P<0.05). Analysis of public available data also suggested that the expression levels of IRF8 mRNA in human DLBCL tissues were inversely correlated with patients' overall survival time. Taken together, this study suggested that IRF8 may play an oncogenic role in human DLBCL by promoting cell proliferation.

show abstract

“…Their new functional roles are constantly being discovered [3]. Importantly, many of these interactions are implicated in human diseases such as cancer or autoimmune disease [4][5][6][7]. Therefore, structure-based studies directed toward the design of completely new or modified receptor-interacting peptides have become a hot spot of current biomedical research.…”

Section: Introductionmentioning

confidence: 99%

Modeling of protein–peptide interactions using the CABS-dock web server for binding site search and flexible docking

Błaszczyk

Kurciński

Kouza

et al. 2016

Methods

144

166

View full text Add to dashboard Cite

Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental and theoretical research. Computational modeling of the structure of protein-peptide interactions is usually divided into two stages: prediction of the binding site at a protein receptor surface, and then docking (and modeling) the peptide structure into the known binding site. This paper presents a comprehensive CABS-dock method for the simultaneous search of binding sites and flexible protein-peptide docking, available as a user's friendly web server. We present example CABS-dock results obtained in the default CABS-dock mode and using its advanced options that enable the user to increase the range of flexibility for chosen receptor fragments or to exclude user-selected binding modes from docking search. Furthermore, we demonstrate a strategy to improve CABS-dock performance by assessing the quality of models with classical molecular dynamics. Finally, we discuss the promising extensions and applications of the CABS-dock method and provide a tutorial appendix for the convenient analysis and visualization of CABS-dock results. The CABS-dock web server is freely available at http://biocomp.chem.uw.edu.pl/CABSdock/.

show abstract

Interferon Regulatory Factor 8 (IRF8) Interacts with the B Cell Lymphoma 6 (BCL6) Corepressor BCOR

Cited by 15 publications

References 42 publications

A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells

Loss of IRF8 Inhibits the Growth of Diffuse Large B-cell Lymphoma

Modeling of protein–peptide interactions using the CABS-dock web server for binding site search and flexible docking

Contact Info

Product

Resources

About