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Int J Biochem Cell Biol ; 128: 105843, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32905854

RESUMEN

The nuclear pore protein NUP62 localizes to spindle poles in mitosis and plays a role in maintaining centrosome homeostasis. In this study, we found that NUP62-depleted cells exhibited a defective spindle assembly checkpoint (SAC) and that depletion of NUP62 caused a slight decrease in MAD2 protein levels after nocodazole treatment. However, depletion of NUP62 did not cause a failure in kinetochore localization of the SAC proteins BUBR1, MAD1, and MAD2 in prometaphase. NUP62 depletion slightly prolonged mitotic timing but did not affect cell doubling time. In addition, NUP62 depletion caused a SAC defect and induced aneuploidy in human neural stem cells. Furthermore, overexpression of NUP62Q391P, a mutant protein causing autosomal recessive infantile bilateral striatal necrosis, resulted in a defect in the SAC, indicating that the amino acid residue Q391 in NUP62 is crucial for its effect on the SAC. Overall, we conclude that NUP62 maintains the SAC downstream of kinetochores and thereby ensures maintenance of chromosomal stability.


Asunto(s)
Puntos de Control del Ciclo Celular , Inestabilidad Cromosómica , Cromosomas Humanos/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Complejo Poro Nuclear/metabolismo , Huso Acromático/metabolismo , Sustitución de Aminoácidos , Cromosomas Humanos/genética , Células HCT116 , Células HeLa , Humanos , Glicoproteínas de Membrana/genética , Mutación Missense , Proteínas de Complejo Poro Nuclear/genética , Huso Acromático/genética
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