Research Papers:

Functional interplay between cylindromatosis and histone deacetylase 6 in ciliary homeostasis revealed by phenotypic analysis of double knockout mice

Jie Ran _, Fan Yu, Juan Qin, Yijun Zhang, Yunfan Yang, Dengwen Li, Jun Zhou and Min Liu

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Oncotarget. 2016; 7:27527-27537. https://doi.org/10.18632/oncotarget.8374

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Jie Ran1,2, Fan Yu2, Juan Qin2, Yijun Zhang2, Yunfan Yang2, Dengwen Li2, Jun Zhou1,2, Min Liu1

1Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance of Shandong Province, Key Laboratory of Molecular and Nano Probes of the Ministry of Education, Shandong Normal University, Jinan 250014, China

2State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China

Correspondence to:

Min Liu, e-mail: [email protected]

Keywords: cylindromatosis, histone deacetylase 6, knockout mouse, cilium, centrosome

Received: February 11, 2016    Accepted: March 16, 2016    Published: March 25, 2016


Cilia are present in most vertebrate tissues with a wide variety of functions, and abnormalities of cilia are linked to numerous human disorders. However, the molecular events underlying ciliary homeostasis are poorly understood. In this study, we generated double knockout (DKO) mice for the deubiquitinase cylindromatosis (CYLD) and histone deacetylase 6 (HDAC6), two critical ciliary regulators. The Cyld/Hdac6 DKO mice were phenotypically normal and showed no obvious variances in weight or behavior compared with their wild-type littermates. Strikingly, Cyld loss-induced ciliary defects in the testis, trachea, and kidney were abrogated in the Cyld/Hdac6 DKO mice. In addition, the diminished α-tubulin acetylation and impaired sonic hedgehog signaling caused by loss of Cyld were largely restored by simultaneous deletion of Hdac6. We further found by immunofluorescence microscopy a colocalization of CYLD and HDAC6 at the centrosome/basal body and, interestingly, loss of Cyld promoted the localization of HDAC6 at the centrosome/basal body. These findings provide physiological insight into the ciliary role of the CYLD/HDAC6 axis and suggest a functional interplay between these two proteins in ciliary homeostasis.

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