Biology:WDR62
 Generic protein structure example |
WD repeat-containing protein 62 is a protein that in humans is encoded by the WDR62 gene.[1][2]
Function
WDR62 is a scaffold protein and interacts with different kinases. WDR62 plays a role in mediating activation of the JNK pathway in response to TNFα. This finding might have implications in the research of TNFα related diseases such as autoimmune diseases and cancer.[3] It has been also shown that WDR62 upregulation can lead to overproliferation of glia cells and potentially glioma and this is coupled with an upregulation in AURKA, AKT, MYC and PI3K signalling.[4]
WDR62 effect on neurogenesis is regulated by MEKK3 in coordination with FBW7 (F-box and WD repeat domain-containing protein 7).[5]
WDR62 has been shown to have a regulatory role on hippocampus development and neurogenesis.[6]
WDR62 is also involved in male spermatogenesis with an essential role in centriole duplication and manchette removal during the spermatogenesis process. The deficiency of WDR62 results in low sperm counts with defected motility, and abnormal morphology.[7]
Clinical significance
Mutations in the WDR62 gene cause of a wide spectrum of severe cerebral cortical malformations including microcephaly,[8] pachygyria with cortical thickening, hypoplasia of the corpus callosum,[1] polymicrogyria as well as microlissencephaly.[9]
Cortical malformation, associated with WDR62 point mutations occurring in humans (V65M and R438H) has been linked to ciliopathies. These WDR62 point mutations drive ciliary disruption in Radial glial cell via disrupting the cilia and centrosome localization of CENPJ and the Intraflagellar transport protein 88 (IFT88), which are required for tubulin requitment to centrosome and transport of tubulin to the cilia tip, respectively.[10]
References
- ↑ 1.0 1.1 "Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations". Nature 467 (7312): 207–210. September 2010. doi:10.1038/nature09327. PMID 20729831. Bibcode: 2010Natur.467..207B.
- ↑ "Entrez Gene: WDR62 WD repeat domain 62". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=284403.
- ↑ "WDR62 mediates TNFα-dependent JNK activation via TRAF2-MLK3 axis". Molecular Biology of the Cell 29 (20): 2470–2480. October 2018. doi:10.1091/mbc.E17-08-0504. PMID 30091641.
- ↑ "Elevated levels of Drosophila Wdr62 promote glial cell growth and proliferation through AURKA signalling to AKT and MYC". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1867 (7): 118713. July 2020. doi:10.1016/j.bbamcr.2020.118713. PMID 32246948.
- ↑ "MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis". PLOS Biology 16 (12): e2006613. December 2018. doi:10.1371/journal.pbio.2006613. PMID 30566428.
- ↑ "An approach to the neurology of aggression". Journal of Psychiatric Research 22 (2): 85–98. September 2020. doi:10.3389/fcell.2020.549353. PMID 3042990.
- ↑ "WDR62 is required for centriole duplication in spermatogenesis and manchette removal in spermiogenesis". Communications Biology 4 (1): 645. May 2021. doi:10.1038/s42003-021-02171-5. PMID 34059773.
- ↑ "Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations". Clinical Genetics 80 (6): 532–540. December 2011. doi:10.1111/j.1399-0004.2011.01686.x. PMID 21496009.
- ↑ "Whole-exome sequencing identifies compound heterozygous mutations in WDR62 in siblings with recurrent polymicrogyria". American Journal of Medical Genetics. Part A 155A (9): 2071–2077. September 2011. doi:10.1002/ajmg.a.34165. PMID 21834044.
- ↑ "The association of microcephaly protein WDR62 with CPAP/IFT88 is required for cilia formation and neocortical development". Human Molecular Genetics 29 (2): 248–263. January 2020. doi:10.1093/hmg/ddz281. PMID 31816041.
Further reading
- "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. September 1996. doi:10.1101/gr.6.9.791. PMID 8889548.
- "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America 101 (33): 12130–12135. August 2004. doi:10.1073/pnas.0404720101. PMID 15302935. Bibcode: 2004PNAS..10112130B.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America 103 (14): 5391–5396. April 2006. doi:10.1073/pnas.0507066103. PMID 16565220. Bibcode: 2006PNAS..103.5391N.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–648. November 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
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