Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene.
Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene.
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DOI：
10.1016/j.cellsig.2009.09.001
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发表时间：
2009-12
影响因子：
4.8
通讯作者：
Pisarska MD
中科院分区：
文献类型：
--
作者：
Kuo FT;Bentsi-Barnes IK;Barlow GM;Bae J;Pisarska MD
Forkhead L2(FOXL2)是Forkhead/HNF3(Forkhead/HNF3)转录因子家族的成员，是颗粒细胞分化的标志--类固醇生成急性调节基因(STAR)的转录抑制因子。FOXL2可能在卵泡成熟过程中发挥作用，防止卵泡早衰导致卵巢早衰。在这项研究中，我们发现FOXL2与Ubc9相互作用，Ubc9是一种E2结合酶，介导苏莫化，这是转录调控的关键机制。FOXL2和Ubc9共同表达于中、小卵泡的颗粒细胞。FOXL2被Ubc9和甲基化，而Ubc9介导的这一SUM化对于FOXL2在STAR启动子上的转录活性是必不可少的。由于FOXL2对颗粒细胞是内源性的，我们建立了一个稳定表达FOXL2的细胞系，发现该细胞系中STAR启动子的活性在Ubc9的存在下显著降低。在FOXL2的25位赖氨酸上发现了苏甲基化位点。赖氨酸25突变为精氨酸导致FOXL2转录抑制活性丧失。综上所述，我们认为Ubc9介导的FOXL2赖氨酸25位的苏莫化是转录抑制STAR基因所必需的，并可能负责控制卵巢卵泡的发育。
Forkhead L2 (FOXL2) is a member of the forkhead/hepatocyte nuclear factor 3 (FKH/HNF3) gene family of transcription factors and acts as a transcriptional repressor of the Steroidogenic Acute Regulatory (StAR) gene, a marker of granulosa cell differentiation. FOXL2 may play a role in ovarian follicle maturation and prevent premature follicle depletion leading to premature ovarian failure. In this study, we found that FOXL2 interacts with Ubc9, an E2-conjugating enzyme that mediates sumoylation, a key mechanism in transcriptional regulation. FOXL2 and Ubc9 are co-expressed in granulosa cells of small and medium ovarian follicles. FOXL2 is sumoylated by Ubc9, and this Ubc9-mediated sumoylation is essential to transcription activity of FOXL2 on the StAR promoter. As FOXL2 is endogenous to granulosa cells, we generated a stable cell line expressing FOXL2 and found that activity of the StAR promoter in this cell line is greatly decreased in the presence of Ubc9. The sumoylation site was identified at lysine 25 of FOXL2. Mutation of lysine 25 to arginine leads to loss of transcriptional repressor activity of FOXL2. Taken together, we propose that Ubc9-mediated sumoylation at lysine 25 of FOXL2 is required for transcriptional repression of the StAR gene and may be responsible for controlling the development of ovarian follicles.
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影响因子：
11.4
作者：
Gostissa, M;Hengstermann, A;Del Sal, G
通讯作者：
Del Sal, G
影响因子：
4.8
作者：
Hong, YL;Rogers, R;Sarge, KD
通讯作者：
Sarge, KD
影响因子：
3.4
作者：
Benayoun, Berenice A.;Auer, Jana;Veitia, Reiner A.
通讯作者：
Veitia, Reiner A.
DOI：
10.1016/s0006-291x(02)00699-x
发表时间：
2002-07-12
影响因子：
3.1
作者：
Jang, MS;Ryu, SW;Kim, E
通讯作者：
Kim, E
影响因子：
4.8
作者：
Bylebyl, GR;Belichenko, I;Johnson, ES
通讯作者：
Johnson, ES