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Publication : MDM1 is a microtubule-binding protein that negatively regulates centriole duplication.

First Author  Van de Mark D Year  2015
Journal  Mol Biol Cell Volume  26
Issue  21 Pages  3788-802
PubMed ID  26337392 Mgi Jnum  J:228434
Mgi Id  MGI:5707092 Doi  10.1091/mbc.E15-04-0235
Citation  Van de Mark D, et al. (2015) MDM1 is a microtubule-binding protein that negatively regulates centriole duplication. Mol Biol Cell 26(21):3788-802
abstractText  Mouse double-minute 1 (Mdm1) was originally identified as a gene amplified in transformed mouse cells and more recently as being highly up-regulated during differentiation of multiciliated epithelial cells, a specialized cell type having hundreds of centrioles and motile cilia. Here we show that the MDM1 protein localizes to centrioles of dividing cells and differentiating multiciliated cells. 3D-SIM microscopy showed that MDM1 is closely associated with the centriole barrel, likely residing in the centriole lumen. Overexpression of MDM1 suppressed centriole duplication, whereas depletion of MDM1 resulted in an increase in granular material that likely represents early intermediates in centriole formation. We show that MDM1 binds microtubules in vivo and in vitro. We identified a repeat motif in MDM1 that is required for efficient microtubule binding and found that these repeats are also present in CCSAP, another microtubule-binding protein. We propose that MDM1 is a negative regulator of centriole duplication and that its function is mediated through microtubule binding.
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