Open AccessDeubiquitylase USP7 regulates human terminal erythroid differentiation by stabilizing GATA1
Author(s) -
Long Liang,
Yuanliang Peng,
Jieying Zhang,
Yibin Zhang,
Mridul Roy,
Xu Han,
Xiaojuan Xiao,
Shuming Sun,
Hong Liu,
Ling Nie,
Yijin Kuang,
Zesen Zhu,
Jinghui Deng,
Yang Xia,
Vijay G. Sankaran,
Christopher D. Hillyer,
Narla Mohandas,
Mao Ye,
Xiuli An,
Jing Liu
Publication year - 2019
Publication title -
haematologica
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2018.206227
Subject(s) - gata1 , ubiquitin , erythropoiesis , proteasome , gene knockdown , microbiology and biotechnology , reticulocyte , small interfering rna , cellular differentiation , biology , chemistry , biochemistry , messenger rna , rna , haematopoiesis , apoptosis , gene , medicine , anemia , stem cell
Ubiquitination is an enzymatic post-translational modification that affects protein fate. The ubiquitin-proteasome system (UPS) was first discovered in reticulocytes where it plays important roles in reticulocyte maturation. Recent studies have revealed that ubiquitination is a dynamic and reversible process and that deubiquitylases are capable of removing ubiquitin from their protein substrates. Given the fact that the UPS is highly active in reticulocytes, it is speculated that deubiquitylases may play important roles in erythropoiesis. Yet, the role of deubiquitylases in erythropoiesis remains largely unexplored. In the present study, we found that the expression of deubiquitylase USP7 is significantly increased during human terminal erythroid differentiation. We further showed that interfering with USP7 function, either by short hairpin RNA-mediated knockdown or USP7-specific inhibitors, impaired human terminal erythroid differentiation due to decreased GATA1 level and that restoration of GATA1 levels rescued the differentiation defect. Mechanistically, USP7 deficiency led to a decreased GATA1 protein level that could be reversed by proteasome inhibitors. Furthermore, USP7 interacts directly with GATA1 and catalyzes the removal of K48-linked poly ubiquitylation chains conjugated onto GATA1, thereby stabilizing GATA1 protein. Collectively, our findings have identified an important role of a deubiquitylase in human terminal erythroid differentiation by stabilizing GATA1, the master regulator of erythropoiesis.