Pathology News

Rual Lab Publishes in The EMBO Journal

By Elizabeth Walker | 19 October

EMBO Journal Publication from the Rual Lab Shows the Role of L3MBTL3 as a Repressor of Notch Signaling

A team led by Drs. Tao Xu and Sung-Soo Park in the Jean-Francois Rual Lab shows that the methyl‐lysine reader L3MBTL3 switches the Notch coactivator RBPJ to a transcriptional repressor by mediating removal of activating histone marks at Notch target genes in mammalian cells, including brain and breast cancer cell lines. In vivo analyses of the homolog of L3MBTL3 in Drosophila melanogaster and Caenorhabditis elegans demonstrate that the functional link between RBPJ and L3MBTL3 is evolutionarily conserved, thus identifying L3MBTL3 as a universal modulator of Notch signaling in metazoans.

This work was performed in collaboration with local U-M laboratories: Yali Dou (Pathology), Cheng-Yu Lee (LSI), Yang Zhang (Bioinformatics), Rork Kuick (Biostatistics), Venkatesha Basrur (Pathology), Alexey Nesvizhskii (Pathology), Kojo Elenitoba-Johnson (Pathology, now University of Pennsylvania) as well as with Tilman Borggrefe (University of Giessen), Rhett A. Kovall (University of Cincinnati), Spyros Artavanis-Tsakonas (Harvard University), and Julian Ceron (L’Hospitalet de Llobregat, Barcelona).

The Rual Lab is now assessing the biomedical relevance of this new molecular mechanism by studying L3MBTL3 KO in mouse models of medulloblastoma, leukemia and breast cancer, three disease contexts in which the putative role of L3MBTL3 as a tumor suppressor remains to be investigated in vivo.

Read the paper, RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1

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