Overexpressed BCL6 (LAZ3) oncoprotein triggers apoptosis, delays S phase progression and associates with replication foci

Albagli, Olivier; Lantoine, D; Quief, Sabine; Quignon, Frédérique; Englert, Christoph; Kerckaert, Jean‐Pierre; Montarras, Didier; Pinset, Christian; Lindon, Catherine

doi:10.1038/sj.onc.1202892

Cited by 61 publications

(78 citation statements)

References 66 publications

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“…Such assumption is supported by the detection of several endogenous components of the replication apparatus within or near the BCL6 bodies (Albagli et al, 1999; this work and data not shown). However, it implies that the interaction between RF and BCL6 bodies precedes the synthesis DNA by the RF.…”

Section: Discussionsupporting

confidence: 55%

“…Human UTA-L cells (Albagli et al, 1999) were grown at 37°C in growth medium (GM) that is a 50/50 mixture of DMEM/F12 medium (Gibco-BRL) containing 10% fetal calf serum (Sigma-Aldrich, Saint Quentin Fallavier, France). The routine culture of the cells was done in GM supplemented gentamycine (PAA, 20 g/ml), tetracycline (Sigma-Aldrich, 2 g/ml), G418 (Gibco-BRL, 500 g/ml), and puromycine (Sigma-Aldrich, 1 g/ml).…”

Section: Materials and Methods Cell Cultures And Nucleic Acid Labelinmentioning

confidence: 99%

“…Reflecting these properties, BCL6 forms nuclear bodies upon overexpression (Albagli et al, 1999(Albagli et al, , 2000Dhordain et al, 1995;Huynh et al, 1998) and shows punctuated distribution at physiological levels of expression (Cattoretti et al, 1995), and is, therefore, also presumed to bundle "distant" sequences when bound to DNA. Looking for the elucidation of the possible role(s) of these BCL6 nuclear bodies, we recently reported that exposition of UTA-L cells, which harbor a tetracycline-regulatory BCL6 allele, to bromodeoxyuridine (BrdU) for increasing pulse periods resulted in the progressive wrapping of the BrdU-containing DNA around BCL6 nuclear bodies (Albagli et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…In normal development, BCL6 is supposed either to protect against, or to trigger, apoptosis depending on cell types and expression levels, to dampen inflammation presumably in part by decreasing the production of certain cytokines in macrophages, to be important for the maintenance of memory T cells, and to be essential for germinal center formation possibly by inhibiting B cell terminal differentiation (Albagli et al, 1999;Albagli-Curiel, 2003;Dent et al, 1997;Fukuda et al, 1997;Ichii et al, 2002;Kojima et al, 2001;Kumagai et al, 1999;Reljic et al, 2000;Tang et al, 2002;Yamochi et al, 1999;Ye et al, 1997;Zhang et al, 2001). More recently, overexpressed BCL6 was also shown to shield mouse embryo fibroblasts against p53-dependent senescence and to improve primary B cell viability in vitro (Shvarts et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

Puvion‐Dutilleul¹,

Souquere-Besse²,

Albagli-Curiel

2003

Microscopy Res & Technique

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BCL6 is a POZ/BTB and zinc finger transcription factor that self-interacts and accumulates into discrete nuclear "bodies" of unknown function. We recently reported that BCL6 bodies associate with bromodeoxyuridine (BrdU)-substituted DNA, suggesting their implication in replication. To examine this possibility, we examine here by electron and confocal microscopy the relation between BCL6 bodies and replication foci (RF) using incorporation of various halogenated nucleotides (BrdU, chlorodeoxyuridine, CldU, and iododeoxyuridine, IdU) or PCNA (proliferating cell nuclear antigen) staining. We show that BCL6 bodies are found associated with RF, as revealed by PCNA staining. However, such association is markedly prolonged upon BrdU or CldU incorporation, but less, or not at all, upon IdU incorporation. Pulse-chase and double-labeling experiments indicate that IdU-substituted DNA leaves BCL6 bodies after a few tenths of minutes while BrdUor CldU-substituted DNA stalls in their vicinity for several hours, thereby giving the characteristic "crowns" of DNA entirely surrounding BCL6 bodies. In all cases, however, the halogenated DNA ends up undergoing a movement from BCL6 bodies toward nucleoplasm and nuclear periphery to reach euchromatin and heterochromatin, respectively. We propose that replicating DNA is prone to be bound by BCL6, while BrdU/CldU incorporation increases this propensity possibly because these two events have synergistic effects on the structure and chromatinisation of the newly synthesized DNA. Finally, despite the known proximity between nuclear sites of transcription and replication, we show via several approaches that BCL6 bodies do not appear to be involved either in RNA synthesis or storage.

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Section: Discussionsupporting

confidence: 55%

Section: Materials and Methods Cell Cultures And Nucleic Acid Labelinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

Puvion‐Dutilleul¹,

Souquere-Besse²,

Albagli-Curiel

2003

Microscopy Res & Technique

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“…With respect to bcl6, the data in the literature indicate that its role as promotor or inhibitor of apoptosis may depend on the cellular context and the experimental approach (37,(41)(42)(43)(44)(45)(46). Some studies reported that bcl6 may protect cells from apoptosis (41,43,45).…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of the bcl6 and CD10 Proteins Is Associated with Increased Apoptosis and Proliferation in Diffuse Large B-Cell Lymphomas

et al. 2003

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There is increasing evidence that bcl6 and CD10 expression may be related to apoptosis and cell cycle progression. Therefore, 79 cases of de novo diffuse large B-cell lymphomas were studied for the expression of bcl6 and CD10 proteins in relation to 1) the apoptotic index; 2) the proliferationassociated proteins Ki67, cyclin A, and cyclin B1; and 3) the expression of the bcl2, p53, Rb, p16, and p27 proteins. Expression of bcl6, CD10, and bcl2 proteins was found in 54/79 (68%), 28/79 (35%), and 47/74 (63%) cases, respectively. The bcl6/CD10 patterns were as follows: bcl6؉/CD10؉ (26 cases, 32%), bcl6؉/CD10-(28 cases, 33%), bcl6؊/CD10؊ (23 cases, 31%), and bcl6؊/CD10؉ (2 cases, 4%). Significant positive correlations were found between bcl6/Ki67 (r ‫؍‬ .328, P ‫؍‬ .003), bcl6/cyclin A (r ‫؍‬ .265, P ‫؍‬ .018), bcl6/apoptotic index (r ‫؍‬ .327, P ‫؍‬ .010), CD10/Ki67 (r ‫؍‬ .296, P ‫؍‬ .008), and CD10/ apoptotic index (r ‫؍‬ .397, P ‫؍‬ .001). In addition, high expression of bcl6 showed significant correlation with negative (null/low) bcl2 expression ( 2 test, P ‫؍‬ .002). The above findings indicate that increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. The association between increased bcl6 expression and enhanced apoptosis might be due, at least in part, to the null/low bcl2 expression because previous in vitro data showed that bcl6 overexpression induces apoptosis accompanied by bcl2 and bcl-xl downregulation. Moreover, significant correlation was found between increased apoptotic index and the bcl6؉/CD10؉ pattern (t test: P ‫؍‬ .014, MannWhitney test: P ‫؍‬ .046). This finding and the positive correlation of the apoptotic index with bcl6 and CD10 expression may be related to previous results showing that the expression of these proteins has favorable effects on the clinical outcome of diffuse large B-cell lymphomas.

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The proto‐oncogene BCL‐6 in normal and malignant B cell development

Niu

2002

Hematological Oncology

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BCL-6 is an important regulator of the immune system. It is required for GC formation and T cell dependent antibody responses. Mice deficient in BCL-6 fail to form GC and mount reduced levels of T cell-dependent antibody responses. BCL-6 (-/-) mice, in addition, develop a massive inflammatory response in many organs characterized by eosinophilic infiltration and hyper-IgE production, a typical Th2 hyperimmune response. This suggests a negative role of BCL-6 in Th2 pathway. The BCL-6 gene encodes a POZ/zinc finger transcription repressor highly expressed in GC B cells, but not in pre-GC B cells or in more differentiated memory or plasma cells. By functioning as a potent transcriptional repressor of various target genes, BCL-6 modulates IL-4, BCR, and CD40L signals for normal B cell development. In B cell lymphomas, structural alterations of the BCL-6 promoter region, including chromosome translocation and somatic hypermutation, represent the most frequent genetic lesions associated with non-Hodgkin lymphoma, especially of diffuse large cell lymphoma, a malignancy often derived from germinal centre (GC) B cells. This suggests that deregulated expression of BCL-6 may contribute to lymphomagenesis.

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Overexpressed BCL6 (LAZ3) oncoprotein triggers apoptosis, delays S phase progression and associates with replication foci

Cited by 61 publications

References 66 publications

The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

Increased Expression of the bcl6 and CD10 Proteins Is Associated with Increased Apoptosis and Proliferation in Diffuse Large B-Cell Lymphomas

The proto‐oncogene BCL‐6 in normal and malignant B cell development

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