- Also known as KELCHL
- Expression Ubiquitous expression in brain (RPKM 3.8), thyroid (RPKM 3.7) and 25 other tissues See more Orthologs mouse all
- Conserved Domains (2) summary
-
- sd00038
Location:340 → 385 - Kelch; KELCH repeat [structural motif]
- cl28614
Location:52 → 592 - BTB; Broad-Complex, Tramtrack and Bric a brac
- sd00038
https://www.ncbi.nlm.nih.gov/pubmed/23455478
- CUL3 and protein kinases: insights from PLK1/KLHL22 interaction. Metzger T, et al. Cell Cycle, 2013 Jul 15. PMID 24067371, Free PMC Article
- KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing. Chen J, et al. Nature, 2018 May. PMID 29769719
- Genome-wide association study of retinopathy in individuals without diabetes. Jensen RA, et al. PLoS One, 2013. PMID 23393555, Free PMC Article
- (Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection. Ferretti LP, et al. Nat Commun, 2016 Aug 26. PMID 27561354, Free PMC Article)
- Ubiquitylation-dependent localization of PLK1 in mitosis. Beck J, et al. Nat Cell Biol, 2013 Apr. PMID 23455478
Nat Cell Biol. 2013 Apr;15(4):430-9. doi: 10.1038/ncb2695. Epub 2013 Mar 3.
Ubiquitylation-dependent localization of PLK1 in mitosis.
Beck J1, Maerki S, Posch M, Metzger T, Persaud A, Scheel H, Hofmann K, Rotin D, Pedrioli P, Swedlow JR, Peter M, Sumara I.Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, 8093 Zurich, Switzerland. Abstract
Polo-like
kinase 1 (PLK1) critically regulates mitosis through its dynamic
localization to kinetochores, centrosomes and the midzone. The polo-box
domain (PBD) and activity of PLK1 mediate its recruitment to mitotic
structures, but the mechanisms regulating PLK1 dynamics remain poorly
understood.
Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and PLK1 kinetochore localization but not PLK1 stability. In the absence of KLHL22, PLK1 accumulates on kinetochores, resulting in activation of the spindle assembly checkpoint (SAC).
CUL3-KLHL22 ubiquitylates Lys 492, located within the PBD, leading to PLK1 dissociation from kinetochore phosphoreceptors. Expression of a non-ubiquitylatable PLK1-K492R mutant phenocopies inactivation of CUL3-KLHL22.
KLHL22 associates with the mitotic spindle and its interaction with PLK1 increases on chromosome bi-orientation. Our data suggest that CUL3-KLHL22-mediated ubiquitylation signals degradation-independent removal of PLK1 from kinetochores and SAC satisfaction, which are required for faithful mitosis.
Here, we identify PLK1 as a target of the cullin 3 (CUL3)-based E3 ubiquitin ligase, containing the BTB adaptor KLHL22, which regulates chromosome alignment and PLK1 kinetochore localization but not PLK1 stability. In the absence of KLHL22, PLK1 accumulates on kinetochores, resulting in activation of the spindle assembly checkpoint (SAC).
CUL3-KLHL22 ubiquitylates Lys 492, located within the PBD, leading to PLK1 dissociation from kinetochore phosphoreceptors. Expression of a non-ubiquitylatable PLK1-K492R mutant phenocopies inactivation of CUL3-KLHL22.
KLHL22 associates with the mitotic spindle and its interaction with PLK1 increases on chromosome bi-orientation. Our data suggest that CUL3-KLHL22-mediated ubiquitylation signals degradation-independent removal of PLK1 from kinetochores and SAC satisfaction, which are required for faithful mitosis.
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