CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells

Abstract Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 l...

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Autores principales:	Zhi Chen, Kun Wang, Canglong Hou, Kaibiao Jiang, Bin Chen, Jianwei Chen, Lifeng Lao, Lie Qian, Guibin Zhong, Zude Liu, Caiguo Zhang, Hongxing Shen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf6e843c9d47433a8fe3986e9567ad83
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spelling	oai:doaj.org-article:bf6e843c9d47433a8fe3986e9567ad832021-12-02T11:40:44ZCRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells10.1038/s41598-017-01344-92045-2322https://doaj.org/article/bf6e843c9d47433a8fe3986e9567ad832017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01344-9https://doaj.org/toc/2045-2322Abstract Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor—p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1, inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4BDCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21Cip1 and regulates cell cycle progression in human osteosarcoma cells.Zhi ChenKun WangCanglong HouKaibiao JiangBin ChenJianwei ChenLifeng LaoLie QianGuibin ZhongZude LiuCaiguo ZhangHongxing ShenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhi Chen Kun Wang Canglong Hou Kaibiao Jiang Bin Chen Jianwei Chen Lifeng Lao Lie Qian Guibin Zhong Zude Liu Caiguo Zhang Hongxing Shen CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
description	Abstract Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor—p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1, inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4BDCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21Cip1 and regulates cell cycle progression in human osteosarcoma cells.
format	article
author	Zhi Chen Kun Wang Canglong Hou Kaibiao Jiang Bin Chen Jianwei Chen Lifeng Lao Lie Qian Guibin Zhong Zude Liu Caiguo Zhang Hongxing Shen
author_facet	Zhi Chen Kun Wang Canglong Hou Kaibiao Jiang Bin Chen Jianwei Chen Lifeng Lao Lie Qian Guibin Zhong Zude Liu Caiguo Zhang Hongxing Shen
author_sort	Zhi Chen
title	CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
title_short	CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
title_full	CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
title_fullStr	CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
title_full_unstemmed	CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
title_sort	crl4bdcaf11 e3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bf6e843c9d47433a8fe3986e9567ad83
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CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells

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