Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation.
Endogenous Cyclin D1 Promotes the Rate of Onset and Magnitude of Mitogenic Signaling via Akt1 Ser473 Phosphorylation.
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DOI：
10.1016/j.celrep.2020.108151
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发表时间：
2020-09-15
期刊：
影响因子：
8.8
通讯作者：
Pestell RG
中科院分区：
文献类型：
--
作者：
Chen K;Jiao X;Di Rocco A;Shen D;Xu S;Ertel A;Yu Z;Di Sante G;Wang M;Li Z;Pestell TG;Casimiro MC;Skordalakes E;Achilefu S;Pestell RG
细胞周期蛋白D1编码磷酸化RB的全酶的调节亚基，并作为协同核癌基因发挥作用。丝氨酸苏氨酸激酶Akt在细胞代谢、存活和促有丝分裂信号传导的控制中起关键作用。在此，乳腺中Akt 1介导的下游底物磷酸化通过细胞周期蛋白D1基因缺失而减少，并且通过乳腺靶向细胞周期蛋白D1过表达而诱导。细胞周期蛋白D1与Akt 1相关，并增加有丝分裂原诱导的发病率和最大细胞Akt 1活性。细胞周期蛋白D1被确定在一个细胞质膜相关池，和细胞质膜定位的细胞周期蛋白D1-但不是核定位的细胞周期蛋白D1-recapitulates Akt 1转录功能。这些研究确定了一种新的细胞周期蛋白D1的细胞核功能，通过增加Akt 1在Ser 473的磷酸化来增强增殖功能。Chen等人表明，细胞周期蛋白D1增强了有丝分裂原诱导的起始速率和最大细胞Akt 1活性。细胞周期蛋白D1结合并磷酸化Akt 1的Ser 473。这些研究确定了一种新的细胞周期蛋白D1的细胞核功能，通过增加Akt 1在Ser 473的磷酸化来增强增殖功能。
Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrates in the mammary gland is reduced by cyclin D1 genetic deletion and is induced by mammary-gland-targeted cyclin D1 overexpression. Cyclin D1 is associated with Akt1 and augments the rate of onset and maximal cellular Akt1 activity induced by mitogens. Cyclin D1 is identified in a cytoplasmic-membrane-associated pool, and cytoplasmic-membrane-localized cyclin D1—but not nuclear-localized cyclin D1—recapitulates Akt1 transcriptional function. These studies identify a novel extranuclear function of cyclin D1 to enhance proliferative functions via augmenting Akt1 phosphorylation at Ser473. Chen et al. show that the rate of onset and maximal cellular Akt1 activity induced by mitogens was augmented by cyclin D1. Cyclin D1 bound and phosphorylated Akt1 at Ser473. These studies identify a novel extranuclear function of cyclin D1 to enhance proliferative functions via augmenting Akt1 phosphorylation at Ser473.
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影响因子：
4.8
作者：
Fu, MF;Rao, M;Pestell, RG
通讯作者：
Pestell, RG
DOI：
10.1107/s0907444910026582
发表时间：
2010-11-01
影响因子：
2.2
作者：
Afonine, Pavel V.;Mustyakimov, Marat;Adams, Paul D.
通讯作者：
Adams, Paul D.
影响因子：
--
作者：
Di Sante G;Di Rocco A;Pupo C;Casimiro MC;Pestell RG
通讯作者：
Pestell RG
DOI：
10.1007/978-1-61779-430-8_16
发表时间：
2012-01-01
期刊：
MTOR: METHODS AND PROTOCOLS
影响因子：
--
作者：
Cybulski, Nadine;Zinzalla, Vittoria;Hall, Michael N.
通讯作者：
Hall, Michael N.
影响因子：
10.5
作者：
Chen, WS;Xu, PZ;Hay, N
通讯作者：
Hay, N