Research Papers:

The B-box module of CYLD is responsible for its intermolecular interaction and cytoplasmic localization

Songbo Xie, Miao Chen, Siqi Gao, Tao Zhong, Peng Zhou, Dengwen Li, Jun Zhou, Jinmin Gao and Min Liu _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:50889-50895. https://doi.org/10.18632/oncotarget.15142

Metrics: PDF 1676 views  |   HTML 1940 views  |   ?  


Songbo Xie1,*, Miao Chen1,*, Siqi Gao2, Tao Zhong1, Peng Zhou1, Dengwen Li2, Jun Zhou1,2, Jinmin Gao2 and Min Liu1

1Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan 250014, China

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

*These authors have contributed equally to this work

Correspondence to:

Min Liu, email: [email protected]

Jinmin Gao, email: [email protected]

Keywords: CYLD, intermolecular interaction, NF-κB, B-box, deubiquitinase

Received: November 30, 2016     Accepted: January 11, 2017     Published: February 07, 2017


The tumor suppressor protein cylindromatosis (CYLD), as a microtubule-associated deubiquitinase, plays a pivotal role in a wide range of cellular activities, including innate immunity, cell division, and ciliogenesis. Structural characterization reveals a small zinc-binding B-box inserted within the ubiquitin specific protease (USP) domain of CYLD; however, the exact role for this module remains yet to be elucidated. Here we identify a critical role for the B-box in facilitating the intermolecular interaction and subcellular localization of CYLD. By co-immunoprecipitation assays we uncover that CYLD has the ability to form an intermolecular complex. Native gel electrophoresis analysis and pull down assays show that the USP domain of CYLD is essential for its intermolecular interaction. Further investigation reveals that deletion of the B-box from the USP domain disrupts the intermolecular interaction of CYLD. Importantly, although loss of the B-box has no obvious effect on the deubiquitinase activity of CYLD, it abolishes the USP domain-mediated retention of CYLD in the cytoplasm. Collectively, these data demonstrate an important role for the B-box module of CYLD in mediating its assembly and subcellular distribution, which might be related to the functions of CYLD in various biological processes.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 15142