UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development

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Protein modification by Ubiquitin (Ub) and Ubiquitin-like proteins (Ubl) plays pivotal roles in a wide range of cellular functions and signaling pathways. The Ufm1 conjugation system is a novel ubiquitin-like system, yet its biological functions and working mechanism remains poorly understood. UFBP1 is a putative Ufm1 target that has been implicated in several signaling pathways but little is known regarding its in vivo function. In this report, by using multiple knockout mouse models, we demonstrate that UFBP1 is essential for murine development and blood cell development. While germ-line deletion of UFBP1 caused defective red blood cell development and embryonic lethality, somatic ablation of UFBP1 impaired production of mature red blood cells and other types of hematopoietic cells. We found that depletion of UFBP1 led to elevated stress in the endoplasmic reticulum that in turn caused cell death of hematopoietic stem cells. Furthermore, UFBP1 deficiency diminished expression of key transcription factors essential for red blood cell development. Taken together, our study provides strong genetic evidence for the essential role of UFBP1 as well as other components of the Ufm1 system in hematopoietic development. Therefore, the ufmylation pathway may represent a novel therapeutic target in treatment of blood diseases.

Vyšlo v časopise: UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005643
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005643

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