Expression and function of a novel isoform of Sox5 in malignant B cells

Edwards, Shanique; Desai, Anand; Liu, Yan; Moore, Cynthia; Xie, Ping

doi:10.1016/j.leukres.2013.12.016

Cited by 12 publications

(20 citation statements)

References 51 publications

(69 reference statements)

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“…Functional evidence and signaling pathway studies indicate that MCC acts as a tumor suppressor gene by inhibiting the oncogenic NF-κB and β-catenin pathways in CRCs and hepatocellular carcinoma [20,27,[31][32][33][34][35][36]. We also previously observed regulation of β-catenin by Sox5, another gene identified in our microarray analysis, in human MM cells [67]. However, NF-κB and β-catenin levels were not altered by knockdown or overexpression of MCC in human MM cells.…”

Section: Signaling Pathways In Human MM Cellssupporting

confidence: 65%

“…All human B cell lines were cultured as described [80]. Most antibodies and reagents used in this study were as previously described [13,67,80]. Mouse monoclonal Abs to MCC were purchased from Santa Cruz were extracted with Illumina GenomeStudio v2011.1, background corrected and variance stabilized in R/Bioconductor using the lumi package [81,82] and modeled in the limma package [83].…”

Section: Mice Cell Lines and Reagentsmentioning

confidence: 99%

“…Lentiviruses of MCC shRNA vectors and a scrambled shRNA vector were packaged following the manufacturer's protocol (Sigma) as previously described [13,89]. Lentiviruses of MCC expression vectors were packaged and titered as previously described [67,80,87]. Human MM cells were transduced with the packaged lentiviruses…”

Section: Lentiviral Packaging and Transduction Of Human MM Cellsmentioning

confidence: 99%

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Regulation of Mitochondria Function by TRAF3 in B Lymphocytes and B Cell Malignancies

Xie¹

2014

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Section: Signaling Pathways In Human MM Cellssupporting

confidence: 65%

Section: Mice Cell Lines and Reagentsmentioning

confidence: 99%

Section: Lentiviral Packaging and Transduction Of Human MM Cellsmentioning

confidence: 99%

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Regulation of Mitochondria Function by TRAF3 in B Lymphocytes and B Cell Malignancies

Xie¹

2014

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“…Lentiviruses of MCC expression vectors were packaged and titered as previously described [67,80,87]. Human MM cells were transduced with the packaged lentiviruses at a MOI of 1:5 (cell:virus) in the presence of 8 μg/ml polybrene [13,87,89].…”

Section: Methodsmentioning

confidence: 99%

Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes

Edwards¹,

Baron²,

Moore³

et al. 2014

J Hematol Oncol

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BackgroundIdentification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized as a tumor suppressor gene in B lymphocytes. The present study aimed to identify novel oncogenes involved in malignant transformation of TRAF3-deficient B cells.MethodsWe used microarray analysis to identify genes differentially expressed in TRAF3−/− mouse splenic B lymphomas. We employed lentiviral vector-mediated knockdown or overexpression to manipulate gene expression in human multiple myeloma (MM) cell lines. We analyzed cell apoptosis and proliferation using flow cytometry, and performed biochemical studies to investigate signaling mechanisms. To delineate protein-protein interactions, we applied affinity purification followed by mass spectrometry-based sequencing.ResultsWe identified mutated in colorectal cancer (MCC) as a gene strikingly up-regulated in TRAF3-deficient mouse B lymphomas and human MM cell lines. Aberrant up-regulation of MCC also occurs in a variety of primary human B cell malignancies, including non-Hodgkin lymphoma (NHL) and MM. In contrast, MCC expression was not detected in normal or premalignant TRAF3−/− B cells even after treatment with B cell stimuli, suggesting that aberrant up-regulation of MCC is specifically associated with malignant transformation of B cells. In elucidating the functional roles of MCC in malignant B cells, we found that lentiviral shRNA vector-mediated knockdown of MCC induced apoptosis and inhibited proliferation in human MM cells. Experiments of knockdown and overexpression of MCC allowed us to identify several downstream targets of MCC in human MM cells, including phospho-ERK, c-Myc, p27, cyclin B1, Mcl-1, caspases 8 and 3. Furthermore, we identified 365 proteins (including 326 novel MCC-interactors) in the MCC interactome, among which PARP1 and PHB2 were two hubs of MCC signaling pathways in human MM cells.ConclusionsOur results indicate that in sharp contrast to its tumor suppressive role in colorectal cancer, MCC functions as an oncogene in B cells. Our findings suggest that MCC may serve as a diagnostic marker and therapeutic target in B cell malignancies, including NHL and MM.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-014-0056-6) contains supplementary material, which is available to authorized users.

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“…Preliminary data from our laboratory also show elevations in the pro‐survival Bcl‐2 family protein Mcl‐1 and the glucose transporter Glut1 in TRAF3 −/− B cells, together with increased glucose utilization (N. Mambetsariev, WL, and GB, unpublished data). A novel isoform of the Sox5 protein was also recently reported in cell lines derived from tumors arising in B‐TRAF3 −/− mice . It will be both interesting and important to investigate the various ways in which TRAF3 restrains B‐cell survival, including how ubiquitin‐related mechanisms might be involved in these pathways.…”

Section: Traf3 As a Regulator Of B‐cell Survivalmentioning

confidence: 82%

TRAF3, ubiquitination, and B‐lymphocyte regulation

Lin

Hostager

Bishop

2015

Immunological Reviews

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Summary The signaling adapter protein tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) is both modified by and contributes to several types of ubiquitination events. TRAF3 plays a variety of context-dependent regulatory roles in all types of immune cells. In B lymphocytes, TRAF3 contributes to regulation of signaling by members of both the TNFR superfamily and innate immune receptors. TRAF3 also plays a unique cell-type-specific and critical role in the restraint of B-cell homeostatic survival, a role with important implications for both B-cell differentiation and the pathogenesis of B-cell malignancies. This review focuses upon the relationship between ubiquitin and TRAF3, and how this contributes to multiple functions of TRAF3 in the regulation of signal transduction, transcriptional activation, and effector functions of B lymphocytes.

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Expression and function of a novel isoform of Sox5 in malignant B cells

Cited by 12 publications

References 51 publications

Regulation of Mitochondria Function by TRAF3 in B Lymphocytes and B Cell Malignancies

Regulation of Mitochondria Function by TRAF3 in B Lymphocytes and B Cell Malignancies

Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes

TRAF3, ubiquitination, and B‐lymphocyte regulation

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