Biomedical subjects

Stéphane Ansieau

Publications and source records attributed to Stéphane Ansieau.

4 recordsLinked to original sources

PubMed2006

New insights into BS69 functions.

The BS69 protein has been commonly described as a co-repressor associated with various transcription factors. However, this hypothesis relied predominantly on overexpression of tagged proteins due to the lack of a reliable BS69 antibody. We present for the first time a complete sequence of BS69 and valuable tools to characterize the endogenous protein. We show that the full-length BS69 protein, as well as minor alternatively spliced isoforms, is ubiquitously expressed, nuclear, and associates with chromatin and mitotic chromosomes. Accordingly, BS69 interacts with a set of chromatin remodeling factors, including ATP-dependent helicases, histone deacetylases, and histone methyltransferases, as well as the E2F6 transcription factor. These data strengthen a role for BS69 in gene repression and link BS69 to chromatin remodeling.

Alternative Splicing↗

PubMed2006

Structure and functional analysis of the MYND domain.

The MYND domain (named after myeloid translocation protein 8, Nervy, and DEAF-1) is a conserved zinc binding domain. It is defined by seven conserved cysteine residues and a single histidine residue that are arranged in a C4-C2HC consensus. MYND domains exist in a large number of proteins that play important roles in development or are associated with cancers and have been shown to mediate protein-protein interactions, mainly in the context of transcriptional regulation. We have determined the three-dimensional structure of the MYND domain from human deformed epidermal autoregulatory factor-1 (DEAF-1). The structure reveals a novel zinc binding fold, in which the C4-C2HC motif forms two sequential zinc binding sites. The first and second zinc binding modules comprise a small beta hairpin and two short alpha helices, respectively. The sequential topology of the two zinc binding sites is distinct from the cross-brace PHD and RING finger folds but has some resemblance to LIM domains. The structure reveals that the MYND domain is a novel member of the treble-clef family of zinc binding domains. The MYND domains of BS69 and BOP bind ligands comprising a PXLXP peptide motif. On the basis of the solution structure of the DEAF-1 MYND domain we calculated a homology model of the MYND domain of the BS69 tumor suppressor. A mutational analysis of the BS69 MYND domain indicates that positively charged residues located on one face of its MYND domain are crucial for the molecular interactions of BS69. Different binding specificities of MYND domains may depend on distinct surface charge distributions.

Amino Acid Sequence↗

PubMed2002

The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene.

The LIM only protein Lmo2 plays an important role in hematopoiesis and leukemogenesis. Lmo2 acts as a bridging molecule between components of hematopoietic gene regulatory protein complexes. We used the yeast two-hybrid system to identify novel Lmo2 interacting proteins and found that the AF6 protein binds to Lmo2. AF6 is a recurrent fusion partner of MLL, the human homolog of Drosophila trithorax chromatin remodeling protein that is involved in childhood leukemia and mixed lineage leukemia. Our data support the notion that recurrent fusion partners of chimeric MLL proteins recruit hematopoietic gene regulatory complexes.

Adaptor Proteins, Signal Transducing↗

PubMed2001

The conserved Mynd domain of BS69 binds cellular and oncoviral proteins through a common PXLXP motif.

BS69 is a transcriptional co-repressor protein and a potential tumor suppressor that binds to the adenoviral oncoprotein E1A. We show that the C-terminal Mynd domain of BS69 (amino acids 516-561) or the closely related Mynd domains of the Caenorhabditis elegans proteins Bra-1 and Bra-2 bind not only to E1A but also to the Epstein-Barr virus EBNA2 oncoprotein and the Myc-related cellular protein MGA. Interaction depends on intact PXLXP motifs present in all three proteins. Moreover, viral proteins compete for binding of BS69 to MGA in a PXLXP-dependent fashion. Because deletions in E1A or EBNA2 that cover the PXLXP motifs are non-transforming, our observations suggest a role for BS69 in cell growth control that is reminiscent of abrogation of the Rb function by various oncoproteins.

Adenoviridae↗