Sumoylation and its regulation in testicular Sertoli cells.

Sumoylation and its regulation in testicular Sertoli cells.
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DOI:
10.1016/j.bbrc.2021.09.066
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发表时间:
2021-11-26
影响因子:
3.1
通讯作者:
Vigodner M
Vigodner M
中科院分区:
生物学4区
文献类型:
--
作者:
Sengupta A;Nanda M;Tariq SB;Kiesel T;Perlmutter K;Vigodner M

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支持细胞的分子调控及其与生殖细胞的相互作用尚未完全明确。SUMO蛋白是正常发育所必需的,在小鼠和人的支持细胞中表达;然而,sumoylation在这些细胞中的细胞特异性作用才刚刚开始被阐明。在其他细胞类型中,包括颗粒细胞,SUMO酰化由SUMO连接酶KAP1/Trim28调节。支持细胞中KAP1的缺失导致睾丸变性;然而,Kap1在这些细胞中的作用尚未被确定。在这里,我们发现小鼠和人的支持细胞都在化学抑制剂或siRNA技术抑制sumoylation后发生凋亡。此外,我们还检测到了sumoylation抑制后Sertoli细胞蛋白质组的变化,我们的数据表明,除其他外,ER/应激相关蛋白的表达受到这种抑制的高度影响。sumo化也可能调节NOTCH信号,这对维持发育中的生殖细胞是重要的。此外,我们发现,在支持细胞衍生的细胞系中,sirna下调KAP1会导致sumoylation几乎完全失活。综上所述,sumoylation调节了Sertoli细胞中重要的生存和信号通路,KAP1可能是这些细胞中sumoylation的主要调节因子。
The molecular regulation of Sertoli cells and their crosstalk with germ cells has not been fully characterized. SUMO proteins are essential for normal development and are expressed in mouse and human Sertoli cells; However, the cell-specific role of sumoylation in those cells has only started to be elucidated. In other cell types, including granulosa cells, sumoylation is regulated by a SUMO ligase KAP1/Trim28. Deletion of KAP1 in Sertoli cells causes testicular degeneration; However, the role of Kap1 in those cells has not been identified. Here we show that both mouse and human Sertoli undergo apoptosis upon inhibition of sumoylation with a chemical inhibitor or via a siRNA technology. We have additionally detected changes in the Sertoli cell proteome upon the inhibition of sumoylation, and our data suggest that among others, the expression of ER/stress-related proteins is highly affected by this inhibition. Sumoylation may also regulate the NOTCH signaling which is important for the maintenance of the developing germ cells. Furthermore, we show that a siRNA-down-regulation of KAP1 in a Sertoli-derived cell line causes an almost complete inactivation of sumoylation. In conclusion, sumoylation regulates important survival and signaling pathways in Sertoli cells, and KAP1 can be a major regulator of sumoylation in these cells.
DOI: 10.1530/rep-15-0239
发表时间: 2016-02
期刊: Reproduction (Cambridge, England)
影响因子: --
作者:
Xiao Y;Pollack D;Andrusier M;Levy A;Callaway M;Nieves E;Reddi P;Vigodner M
通讯作者: Vigodner M
DOI: 10.1530/rep-09-0492
发表时间: 2010-06-01
期刊: REPRODUCTION
影响因子: 3.8
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DOI: 10.1016/j.bbrc.2006.04.177
发表时间: 2006-07-07
影响因子: 3.1
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通讯作者: Kondo, Takashi
DOI: 10.1093/humrep/des317
发表时间: 2013-01-01
期刊: HUMAN REPRODUCTION
影响因子: 6.1
作者:
Vigodner, Margarita;Shrivastava, Vibha;Callaway, Myrasol
通讯作者: Callaway, Myrasol