| Literature DB >> 30718289 |
Evangelia Koutelou1,2,3, Li Wang4,2,3,5,6, Andria C Schibler4,2,3,6,7, Hsueh-Ping Chao4,2,3,5,6, Xianghong Kuang4,2,3, Kevin Lin4,2,3, Yue Lu4,2,3, Jianjun Shen4,2,3,6, Collene R Jeter4,2,3, Andrew Salinger4,2,3, Marenda Wilson8, Yi Chun Chen6,7,8, Boyko S Atanassov4,2,3, Dean G Tang4,2,3, Sharon Y R Dent1,2,3,6.
Abstract
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 TGFβ 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.Entities:
Keywords: Endothelial cells; Mouse; Pericytes; Placenta; RTK receptors; SAGA; TGFβ signaling; USP22; Vascular development
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Year: 2019 PMID： 30718289 PMCID： PMC6398448 DOI： 10.1242/dev.174037
Source DB: PubMed Journal: Development ISSN： 0950-1991 Impact factor: 6.868