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细胞质 ASPP1 通过控制 YAP 抑制细胞凋亡。

Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP.

机构信息

The Beatson Institute for Cancer Research, Bearsden, Glasgow G61 1BD, United Kingdom.

出版信息

Genes Dev. 2010 Nov 1;24(21):2430-9. doi: 10.1101/gad.1954310.

DOI:10.1101/gad.1954310
PMID:21041411
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2964753/
Abstract

The ASPP (apoptosis-stimulating protein of p53) family of proteins can function in the nucleus to modulate the transcriptional activity of p53, with ASPP1 and ASPP2 contributing to the expression of apoptotic target genes. In this study, we describe a new function for cytoplasmic ASPP1 in controlling YAP (Yes-associated protein)/TAZ. ASPP1 can inhibit the interaction of YAP with LATS1 (large tumor suppressor 1), a kinase that phosphorylates YAP/TAZ and promotes cytoplasmic sequestration and protein degradation. This function of ASPP1 therefore enhances nuclear accumulation of YAP/TAZ and YAP/TAZ-dependent transcriptional regulation. The consequence of YAP/TAZ activation by ASPP1 is to inhibit apoptosis, in part through the down-regulation of Bim expression, leading to resistance to anoikis and enhanced cell migration. These results reveal a potential oncogenic role for cytoplasmic ASPP1, in contrast to the tumor-suppressive activity described previously for nuclear ASPP1.

摘要

ASPP（p53 的凋亡刺激蛋白）家族蛋白可在核内发挥作用，调节 p53 的转录活性，其中 ASPP1 和 ASPP2 有助于凋亡靶基因的表达。在这项研究中，我们描述了细胞质 ASPP1 在控制 YAP（Yes 相关蛋白）/TAZ 中的新功能。ASPP1 可以抑制 YAP 与 LATS1（大肿瘤抑制因子 1）的相互作用，LATS1 是一种使 YAP/TAZ 磷酸化并促进细胞质隔离和蛋白降解的激酶。因此，ASPP1 的这种功能增强了 YAP/TAZ 和 YAP/TAZ 依赖性转录调控的核积累。ASPP1 通过激活 YAP/TAZ 产生的后果是抑制细胞凋亡，部分原因是下调 Bim 表达，导致对失巢凋亡的抵抗和增强的细胞迁移。这些结果揭示了细胞质 ASPP1 的潜在致癌作用，与先前描述的核 ASPP1 的肿瘤抑制活性形成对比。

相似文献

[1]
Cytoplasmic ASPP1 inhibits apoptosis through the control of YAP.

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[2]
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[4]
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[7]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1.

Genes Dev. 2010-11-1

[2]
ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development.

Dev Cell. 2010-7-8

[3]
ASPP2 regulates epithelial cell polarity through the PAR complex.

Curr Biol. 2010-7-8

[4]
The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version.

Genes Dev. 2010-5

[5]
A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP).

Genes Dev. 2010-1-1

[6]
Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region- containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma.

Hepatology. 2010-1

[7]
The dASPP-dRASSF8 complex regulates cell-cell adhesion during Drosophila retinal morphogenesis.

Curr Biol. 2009-12-15

[8]
New insights into the expanding complexity of the tumor suppressor ASPP2.

Cell Cycle. 2009-9-15

[9]
Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling.

Biofactors. 2009

[10]
Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds.

Proc Natl Acad Sci U S A. 2009-3-17

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