Abstract
Mitosis is a precisely regulated cellular mechanism that governs fundamental processes like embryogenesis, development, and tissue regeneration. Prenatal mitotic errors can cause birth defects, including neurodevelopmental disorders, congenital heart disease, and miscarriage, whereas postnatal abnormal cell division leads to early tissue aging and tumorigenesis. Aberrant expression of the serine/threonine kinase, TANK-Binding Kinase 1 (TBK1), is associated with several types of cancers, such as glioblastomas, breast, and lung cancers. However, its role in normal cell division is not well understood. To better define mechanistically how TBK1 is activated during mitosis, we identified NAK-associated protein 1 (NAP1/AZI2) to be essential for mitosis. Loss of NAP1 reduces mitosis and cell proliferation resulting in the accumulation of multinucleated cells phenocopying the loss of TBK1. NAP1 is further responsible for the activation of TBK1 at centrosomes of dividing cells and required for proper mitotic progression. Furthermore, NAP1 expression during mitosis is mediated by the ubiquitin proteasome system. We have uncovered a distinct function for the NAP1-TBK1 complex during mitosis, completely novel from its previously known function in innate immunity.
Competing Interest Statement
The authors have declared no competing interest.