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Publication : USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta.

First Author  Koutelou E Year  2019
Journal  Development Volume  146
Issue  4 PubMed ID  30718289
Mgi Jnum  J:272613 Mgi Id  MGI:6284202
Doi  10.1242/dev.174037 Citation  Koutelou E, et al. (2019) USP22 controls multiple signaling pathways that are essential for vasculature formation in the mouse placenta. Development 146(4):dev174037
abstractText  USP22, a component of the SAGA complex, is overexpressed in highly aggressive cancers, but the normal functions of this deubiquitinase are not well defined. We determined that loss of USP22 in mice results in embryonic lethality due to defects in extra-embryonic placental tissues and failure to establish proper vascular interactions with the maternal circulatory system. These phenotypes arise from abnormal gene expression patterns that reflect defective kinase signaling, including TGFbeta and several receptor tyrosine kinase pathways. USP22 deletion in endothelial cells and pericytes that are induced from embryonic stem cells also hinders these signaling cascades, with detrimental effects on cell survival and differentiation as well as on the ability to form vessels. Our findings provide new insights into the functions of USP22 during development that may offer clues to its role in disease states.
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