Ambivalent role of BCL6 in cell survival and transformation.
The BCL6 gene is often structurally altered and probably 'misregulated' in two different types of human B-cell non-Hodgkin lymphomas (BNHL) thought to arise from germinal centre B cells. BCL6 encodes a BTB/POZ and zinc finger protein whose biochemical properties support a role as a DNA-binding transcriptional repressor and disclose, in part, the underlying mechanisms. In contrast, the study of the 'oncogenic' structural alterations of BCL6 in BNHL and of its cellular functions gives rise to much more heterogeneous data with no obvious unifying picture so that how and even whether BCL6 contributes to lymphomagenesis remains unclear. This review will summarize the current knowledge about the 'oncogenic' alterations and cellular functions of BCL6 and, based on some results, will propose the following hypotheses: (1) In various systems, including in memory T cells and also in germinal centre B cells and possibly in certain postmitotic cells, BCL6 may act by stabilizing a particular stage of differentiation. (2) Both its ambivalent effects on cell survival and the heterogeneous consequences of its alterations in BNHL suggest that BCL6 can be oncogenic not only upon overexpression or persistent expression, as often proposed, but also, similar to some of its relatives, upon 'accidental' downregulation.
Albagli-Curiel
Olivier
O
CNRS UPR 1983, Institut André Lwoff, Villejuif, France. olivier.albagli@ujf-grenoble.fr
D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors