The tumor suppressor CYLD regulates microtubule dynamics and plays a role in cell migration.
The familial cylindromatosis tumor suppressor CYLD is known to contain three cytoskeleton-associated protein glycine-rich (CAP-Gly) domains, which exist in a number of microtubule-binding proteins and are responsible for their association with microtubules. However, it remains elusive whether CYLD interacts with microtubules and, if so, whether the interaction is mediated by the CAP-Gly domains. In this study, our data demonstrate that CYLD associates with microtubules both in cells and in vitro, and the first CAP-Gly domain of CYLD is mainly responsible for the interaction. Knockdown of cellular CYLD expression dramatically delays microtubule regrowth after nocodazole washout, indicating an activity for CYLD in promoting microtubule assembly. Our data further demonstrate that CYLD enhances tubulin polymerization into microtubules by lowering the critical concentration for microtubule assembly. In addition, we have identified by wound healing assay a critical role for CYLD in mediating cell migration and found that its first CAP-Gly domain is required for this activity. Thus CYLD joins a growing list of CAP-Gly domain-containing proteins that regulate microtubule dynamics and function.
Gao
Jinmin
J
Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, China.
Huo
Lihong
L
Sun
Xiaoou
X
Liu
Min
M
Li
Dengwen
D
Dong
Jin-Tang
JT
Zhou
Jun
J
D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D000074749:Deubiquitinating Enzyme CYLD; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D050257:Tubulin Modulators; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D014404:Tubulin; D050257:Tubulin Modulators; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D015739:Nocodazole