Functions of NIFK, a Ki67 interacting protein, in cell cycle progression, p53 signaling and ribosome biogenesis
Date Issued
2015
Date
2015
Author(s)
Pan, Wen-An
Abstract
Coupled cell growth and division is critical for cell proliferation. Emerging studies suggest that the integrity of ribosome biogenesis is essential for the coordination of cell growth and division, while its dysregulation is associated with human diseases including cancer and ribosomopathies. Ribosome biogenesis governs protein synthesis. NIFK is transactivated by c-Myc, the key regulator of ribosome biogenesis. The biological function of human NIFK is not well established, except that it has been shown to interact with Ki-67 and NPM1. Here we report that NIFK is required for cell cycle progression and participates in the ribosome biogenesis via its RNA recognition motif (RRM). We show that silencing of NIFK inhibits cell proliferation through a reversible p53-dependent G1 arrest, possibly by induction of the RPL5/RPL11-mediated nucleolar stress. Mechanistically it is the consequence of impaired maturation of 28S and 5.8S rRNA resulting from inefficient cleavage of internal transcribed spacer (ITS) 1, a critical step in the separation of pre-ribosome to small and large subunits. Complementation of NIFK silencing by mutants shows that RNA-binding ability of RRM is essential for the pre-rRNA processing and G1 progression. More specifically, we validate that the RRM of NIFK preferentially binds to the position in the 5’-end of ITS2 rRNA, likely in both sequence specific and secondary structure dependent manners. Our results show how NIFK is involved in cell cycle progression through RRM-dependent pre-rRNA maturation, which could enhance our understanding of the function of NIFK in cell proliferation, and potentially also cancer and ribosomopathies.
Subjects
cell cycle
rRNA processing
nucleolar stress
ribosome biogenesis
RNA recognition motif (RRM)
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-104-D97b46013-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):144015206391f5e2e5fb7bdd093dbb54