ISSN: 1838-7640Theranostics
Global reach, higher impact
Theranostics 2022; 12(11):5051-5068. doi:10.7150/thno.72365 This issue Cite
Research Paper
CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1
1. Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Department of Biology, and Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, 518055, China.
2. Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, 999077, China.
3. Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
4. Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261 USA.
Citation:
Lu Y, Mu Y, Chen J, Guan X, Guo L, Wu C. CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1. Theranostics 2022; 12(11):5051-5068. doi:10.7150/thno.72365. https://www.thno.org/v12p5051.htm
Other stylesAbstract
Background: p53 deficiency is a key causal factor for tumor development and progression. p53 acts in this process through, at least in part, cooperation with YAP1 but the underlying molecular mechanism is incompletely understood. In this paper, we show that CLP36, an actinin-binding cytoskeletal protein, links p53 deficiency to up-regulation of YAP1 expression and sarcoma progression.
Methods: Immunohistochemical staining and Western blotting were used to investigate the effect of p53 deficiency on CLP36 expression in sarcoma tissues and cells. Furthermore, molecular, cellular, and genetic knockout and knockdown approaches were employed to investigate the functions of CLP36 in regulation of sarcoma cell behavior in culture and tumor growth in mice. Finally, biochemical approaches were used to investigate the molecular mechanism by which CLP36 regulates the malignant behavior of p53 deficient sarcoma cells.
Results: We have found that the expression of CLP36 is up-regulated in response to loss of p53 in sarcoma tissues and cells. Depletion of CLP36 inhibited malignant behavior of p53 deficient sarcoma cells. Furthermore, knockout of CLP36 in mice markedly inhibited p53 deficiency-induced tumorigenesis and improved the survival of the p53 deficient mice. Mechanistically, CLP36 promoted p53 deficiency-induced tumorigenesis through inhibition of E3 ligase atrophin-1 interacting protein-4 (AIP-4)-dependent proteasomal degradation of YAP1 and consequently increase of YAP1 expression.
Conclusions: Our results reveal a crucial role of CLP36 in linking p53 deficiency to up-regulation of YAP1 expression and sarcoma progression. Our findings suggest that therapeutic targeting the CLP36/YAP1 signaling axis may provide an effective strategy for alleviation of p53 deficient sarcoma progression.
Keywords: Sarcoma, CLP36, p53, YAP1, AIP-4
Citation styles
APA
Lu, Y., Mu, Y., Chen, J., Guan, X., Guo, L., Wu, C. (2022). CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1. Theranostics, 12(11), 5051-5068. https://doi.org/10.7150/thno.72365.
ACS
Lu, Y.; Mu, Y.; Chen, J.; Guan, X.; Guo, L.; Wu, C. CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1. Theranostics 2022, 12 (11), 5051-5068. DOI: 10.7150/thno.72365.
NLM
Lu Y, Mu Y, Chen J, Guan X, Guo L, Wu C. CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1. Theranostics 2022; 12(11):5051-5068. doi:10.7150/thno.72365. https://www.thno.org/v12p5051.htm
CSE
Lu Y, Mu Y, Chen J, Guan X, Guo L, Wu C. 2022. CLP36 promotes p53 deficient sarcoma progression through suppression of atrophin-1 interacting protein-4 (AIP-4)-dependent degradation of YAP1. Theranostics. 12(11):5051-5068.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.