Tumour suppressor CYLD is a negative regulator of the mitotic kinase Aurora-B.

Abstract

The familial cylindromatosis tumour suppressor CYLD contains three cytoskeleton-associated protein glycine-rich (CAP-Gly) domains and a deubiquitinase domain. The tumour-suppressing function of CYLD has been attributed to its deubiquitinase domain, which removes lysine-63-linked polyubiquitin chains from target proteins, leading to the inhibition of cell survival and proliferation. In this study, we have detected an interaction of CYLD with the mitotic kinase Aurora-B. The interaction is mediated by the third CAP-Gly domain of CYLD and results in suppression of Aurora-B activity. Mechanistic studies reveal that the inhibition of Aurora-B activity by CYLD is independent of its deubiquitinase activity. Instead, CYLD interacts with protein phosphatase 2A (PP2A) and promotes the ability of PP2A to bind and dephosphorylate Aurora-B at threonine-232. Cylindromatosis-associated truncating mutations of CYLD abolish its interaction with PP2A, its enhancing effect on the PP2A/Aurora-B interaction, and its inhibitory effect on Aurora-B activity. These findings uncover Aurora-B and PP2A as novel binding partners of CYLD and suggest that CYLD negatively regulates Aurora-B activity through acting on the PP2A axis.

• Authors: Lei Sun, Jinmin Gao, Lihong Huo, Xiaoou Sun, Xingjuan Shi, Min Liu, Dengwen Li, Chuanmao Zhang, Jun Zhou
• Journal: The Journal of pathology (J Pathol) Vol. 221 Issue 4 Pg. 425-32 (Aug 2010) ISSN: 1096-9896 [Electronic] England
• PMID: 20593489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Suppressor Proteins
• AURKB protein, human
• Aurora Kinase B
• Aurora Kinases
• Protein Serine-Threonine Kinases
• Protein Phosphatase 2
• CYLD protein, human
• Deubiquitinating Enzyme CYLD

Topics

• Aurora Kinase B
• Aurora Kinases
• Cells, Cultured
• Deubiquitinating Enzyme CYLD
• Gene Knockdown Techniques
• HeLa Cells
• Humans
• Microscopy, Fluorescence
• Phosphorylation
• Protein Phosphatase 2 (metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Tumor Suppressor Proteins (genetics, metabolism, physiology)