Ubiquitin specific protease 21 is dispensable for normal development, hematopoiesis and lymphocyte differentiation.
Ubiquitin specific protease 21 is dispensable for normal development, hematopoiesis and lymphocyte differentiation.
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DOI：
10.1371/journal.pone.0117304
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nijnik A
中科院分区：
文献类型：
--
作者：
Pannu J;Belle JI;Förster M;Duerr CU;Shen S;Kane L;Harcourt K;Fritz JH;Clare S;Nijnik A
USP21 是一种泛素特异性蛋白酶，可催化蛋白质去泛素化，但其生理底物的鉴定仍然具有挑战性。已知 USP21 在体外可使转录因子 GATA3 和死亡域激酶 RIPK1 去泛素化，但这种调节在体内发挥重要生物学作用的情况仍不清楚。为了确定 USP21 是否是体内 GATA3 或 RIPK1 活性的必需且非冗余的调节因子，我们对 Usp21 缺陷小鼠进行了表征，重点关注小鼠的活力和发育、造血干细胞功能和淋巴细胞分化。研究发现，Usp21 敲除小鼠具有存活能力和生育能力，没有明显的形态异常，而 GATA3 和 RIPK1 敲除小鼠系表现出胚胎或围产期致死性。 USP21的缺失对造血干细胞功能、淋巴细胞发育或抗原呈递细胞对TLR和TNFR刺激的反应也没有影响。造血干细胞或T淋巴细胞中的GATA3水平保持不变。我们观察到老年 Usp21 敲除小鼠表现出自发性 T 细胞激活，但这与受影响细胞中 GATA3 水平的改变无关。 Usp21 敲除系与先前表征的 GATA3 和 RIPK1 敲除小鼠的表型对比强烈表明，USP21 对于小鼠发育过程中、造血干细胞和淋巴细胞分化过程中 GATA3 和 RIPK1 活性的调节是多余的。本研究中鉴定的 Usp21 缺陷小鼠系可能作为未来表征 USP21 生理功能的有用工具。
USP21 is a ubiquitin specific protease that catalyzes protein deubiquitination, however the identification of its physiological substrates remains challenging. USP21 is known to deubiquitinate transcription factor GATA3 and death-domain kinase RIPK1 in vitro, however the in vivo settings where this regulation plays a biologically significant role remain unknown. In order to determine whether USP21 is an essential and non-redundant regulator of GATA3 or RIPK1 activity in vivo, we characterized Usp21-deficient mice, focusing on mouse viability and development, hematopoietic stem cell function, and lymphocyte differentiation. The Usp21-knockout mice were found to be viable and fertile, with no significant dysmorphology, in contrast to the GATA3 and RIPK1 knockout lines that exhibit embryonic or perinatal lethality. Loss of USP21 also had no effect on hematopoietic stem cell function, lymphocyte development, or the responses of antigen presenting cells to TLR and TNFR stimulation. GATA3 levels in hematopoietic stem cells or T lymphocytes remained unchanged. We observed that aged Usp21-knockout mice exhibited spontaneous T cell activation, however this was not linked to altered GATA3 levels in the affected cells. The contrast in the phenotype of the Usp21-knockout line with the previously characterized GATA3 and RIPK1 knockout mice strongly indicates that USP21 is redundant for the regulation of GATA3 and RIPK1 activity during mouse development, in hematopoietic stem cells, and in lymphocyte differentiation. The Usp21-deficient mouse line characterized in this study may serve as a useful tool for the future characterization of USP21 physiological functions.
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影响因子：
64.8
作者：
Skarnes WC;Rosen B;West AP;Koutsourakis M;Bushell W;Iyer V;Mujica AO;Thomas M;Harrow J;Cox T;Jackson D;Severin J;Biggs P;Fu J;Nefedov M;de Jong PJ;Stewart AF;Bradley A
通讯作者：
Bradley A
DOI：
10.1126/science.1224026
发表时间：
2012-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bogunovic D;Byun M;Durfee LA;Abhyankar A;Sanal O;Mansouri D;Salem S;Radovanovic I;Grant AV;Adimi P;Mansouri N;Okada S;Bryant VL;Kong XF;Kreins A;Velez MM;Boisson B;Khalilzadeh S;Ozcelik U;Darazam IA;Schoggins JW;Rice CM;Al-Muhsen S;Behr M;Vogt G;Puel A;Bustamante J;Gros P;Huibregtse JM;Abel L;Boisson-Dupuis S;Casanova JL
通讯作者：
Casanova JL
影响因子：
30.8
作者：
PANDOLFI, PP;ROTH, ME;LINDENBAUM, MH
通讯作者：
LINDENBAUM, MH
影响因子：
16
作者：
Ea, CK;Deng, L;Chen, ZJJ
通讯作者：
Chen, ZJJ
影响因子：
4.4
作者：
Kim, KI;Malakhova, OA;Zhang, DE
通讯作者：
Zhang, DE