TY - JOUR
T1 - CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72
AU - Ying, Zhenguang
AU - Wang, Kaifang
AU - Wu, Junfeng
AU - Wang, Mingyu
AU - Yang, Jing
AU - Wang, Xia
AU - Zhou, Guowei
AU - Chen, Haibin
AU - Xu, Hongwu
AU - Sze, Stephen Cho Wing
AU - Gao, Feng
AU - Li, Chunman
AU - Sha, Ou
N1 - Publisher Copyright:
© The Author(s) 2022.
PY - 2022/12
Y1 - 2022/12
N2 - Background: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored.Results: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage.Conclusion: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.
AB - Background: The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored.Results: We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage.Conclusion: We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.
KW - Astrin
KW - CCHCR1
KW - Centrosome
KW - CEP72
KW - Microtubule organization
KW - Mitosis
UR - http://www.scopus.com/inward/record.url?scp=85140569107&partnerID=8YFLogxK
U2 - 10.1186/s12915-022-01437-6
DO - 10.1186/s12915-022-01437-6
M3 - Journal article
C2 - 36280838
AN - SCOPUS:85140569107
SN - 1741-7007
VL - 20
JO - BMC Biology
JF - BMC Biology
IS - 1
M1 - 240
ER -
