RACK1 Prevents the Premature Differentiation of Epidermal Progenitor Cells by Inhibiting IRF6 Expression.
RACK1 Prevents the Premature Differentiation of Epidermal Progenitor Cells by Inhibiting IRF6 Expression.
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DOI：
10.1016/j.jid.2021.10.017
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发表时间：
2022-05
影响因子：
6.5
通讯作者：
Sen, George L.
中科院分区：
文献类型：
--
作者：
Ling, Ji;Tiwari, Manisha;Chen, Yifang;Sen, George L.
为了适当地维持屏障功能，位于皮肤基底层中的表皮干细胞和祖细胞持续增殖和分化以贡献于最外层。干细胞自我更新和分化之间平衡的扰动导致各种皮肤疾病（Blanpain和Fuchs，2009）。因此，了解决定基底层细胞命运的因素至关重要。我们和其他人已经鉴定了IRF 6、ZNF 750、KLF 4和GRHL 3作为将基底层细胞转变为分化细胞所必需的转录因子（Oberbeck et al.，2019年，塞格雷等人，1999年，Sen等人，2012年，Ting等人，2005年）。然而，很少有人知道这些转录因子的水平是如何调节，以防止干细胞和祖细胞的过早分化。为了鉴定在表皮祖细胞中富集的推定因子，我们挖掘了我们以前的基因表达谱数据，比较了未分化和分化的原代人角质形成细胞（Sen et al.，2010年）。有趣的是，活化的C激酶1的受体也称为RACK 1（GNB2L1）在表皮分化后高度下调。RACK 1是含有WD 40的支架蛋白，其最初被鉴定为活化的蛋白激酶C的锚定蛋白（罗恩等人，1994年）。作为一种支架蛋白，已发现它与多种蛋白质相关，影响广泛的细胞过程（Li和Xie，2015）。RACK 1基因敲除小鼠在原肠胚形成阶段是胚胎致死的，这排除了在正常组织中进一步检查RACK 1
To properly maintain barrier function, epidermal stem and progenitor cells, which reside in the basal layer of the skin, continually proliferate and differentiate to contribute to the outermost layers. Perturbations in the balance between stem cell self-renewal and differentiation leads to a variety of skin disorders (Blanpain and Fuchs, 2009). Thus, it is critical to understand the factors that govern basal layer cell fate decisions. We and others have identified IRF6, ZNF750, KLF4, and GRHL3 as transcription factors necessary to transition basal layer cells to a differentiated one (Oberbeck et al., 2019, Segre et al., 1999, Sen et al., 2012, Ting et al., 2005). However, less is known about how the levels of these transcription factors are regulated to prevent premature differentiation of stem and progenitor cells. To identify putative factors enriched in epidermal progenitor cells, we mined our previous gene expression profiling data comparing undifferentiated and differentiated primary human keratinocytes (Sen et al., 2010). Interestingly, the receptor for activated C kinase 1 also known as RACK1 (GNB2L1) was highly downregulated upon epidermal differentiation.RACK1 is a WD40 containing scaffolding protein that was originally identified as an anchoring protein for activated protein kinase C (Ron et al., 1994). As a scaffolding protein, it has been found to be associated with a large variety of proteins to affect a wide range of cellular processes (Li and Xie, 2015). RACK1 knockout mice are embryonic lethal at the gastrulation stage, which has precluded further examination of RACK1 in normal tissue
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影响因子：
64.8
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
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Ma'ayan A
影响因子：
56.9
作者：
Ting, SB;Caddy, J;Jane, SM
通讯作者：
Jane, SM
影响因子：
11.8
作者：
Sen, George L.;Boxer, Lisa D.;Webster, Dan E.;Bussat, Rose T.;Qu, Kun;Zarnegar, Brian J.;Johnston, Danielle;Siprashvili, Zurab;Khavari, Paul A.
通讯作者：
Khavari, Paul A.
影响因子：
64.8
作者：
Oberbeck, Nina;Pham, Victoria C.;Dixit, Vishva M.
通讯作者：
Dixit, Vishva M.