. 2015 Jun;240(6):774–786. doi: 10.1177/1535370215579168

Table 1.

The role of NPM in proliferative cells.

Interaction	Effect on/Function of NPM	Effect on the cell	Reference
Ribosome biogenesis
TTF-1	Imports TTF-1 into the nucleolus	rRNA transcription	21
pre-47S rRNA	Cleaves ITS2 of 32s rRNA	Maturation of 28S rRNA	7, 8
CDK1, B23.2, NPM3	Phosphorylation by CDK1 and/or heterotrimerization with B23.2 or NPM2 inhibits NPM RNA binding activity	Inhibition of 28S maturation	11, 13
ARF	Sumoylation of NPM	NPM nucleolar localization and protection from caspase-3 cleavage	23, 24
ARF	Sumoylation of NPM	Inhibition of 28S maturation	23, 24
Senp3	Reverses ARF sumoylation	Maturation of 28S rRNA	24
PARP-1 and PARP-2	PARP-1, PARP-2 and NPM extruded from nucleolus together following inhibition of RNA Pol I	rRNA quality control	9
APE1/Ref1	Stimulates APE1 endonuclease activity on abasic dsDNA but reduces activity on ssRNA	rRNA quality control	8
40S and 60S ribosomal subunits	Transport and export of ribosomal subunits to cytoplasm	Ribosome production	3, 16, 17
CRM1 complex	Transport and export of ribosomal subunits to cytoplasm	Ribosome production	3, 16, 17
CK2	Phosphorylation by CK2 promotes dissociation of substrate bound to NPM	Inhibition of NPM chaperone activity	15
Centrosome duplication
Centrosome	Bound to unduplicated centrosomes between pairs of centrioles	Inhibition of centrosome duplication and centriole pairing	4, 26, 27, 30
Cyclin E/CDK1	Phosphorylation by Cyclin E/CDK1 promotes dissociation of NPM from centrosomes	Centrosome duplication	26, 27
Crm1	Reassociates with centrosomes via Crm1	Inhibition of centrosome duplication	4, 26, 30
ROCK II	Interacts with ROCK II at centrosomes following Cyclin E/CDK2 phosphorylation	Increased ROCK II kinase activity	28
Oxidative stress and DNA damage
p53	Stabilizes p53	Increased p53 transcriptional activity	35, 38, 39
p53	Inhibits p53	Protects against stress-induced apoptosis in normal and malignant hematopoietic cells
p53 and ATR	Represses p53 and inhibits ATR phosphorylation of p53	Sets the threshold for p53 response to UV-induced stress
MDM2	Inhibits MDM2 following UV-induced damage	Stabilizes p53	37
p21	Negatively regulates p21 ubiquitination	Stabilizes p21	40
ARF	Interacts with ARF in nucleoli	Stabilizes ARF	44, 45, 46, 49
ARF	Interacts with ARF in nucleoli	Inhibits ARF targeting of MDM2	44, 45, 46, 49
Akt	Phosphorylation by Akt following DNA damage disrupts interaction with ARF	Inhibition of MDM2 and stabilization of p53	49, 50
pRb and E2F1	Sumoylated NPM interacts with hyperphosphorylated pRb in nucleoli during late S-phase/early G₂	Increased E2F1 transcriptional activity	23, 54, 55
pRb and E2F1	Upon UV-induced damage, phosphorylated NPM associates with pRb, blocking repression of E2F1	Increased E2F1 transcriptional activity	23, 54, 55
GADD45α	Regulates nuclear import of GADD45α	Inhibition of G2/M transition of the cell cycle	43
MnSOD	Co-activator with NF-κB to induce expression of MnSOD following treatment with PMA and cytokines	Regulation of MnSOD expression	94
Regulation of apoptosis
PI(3,4,5)P3	Inhibits CAD	Blocks DNA fragmentation	23, 56-58
Akt2	Nuclear Akt2 protects unsumoylated NPM from caspase-3 cleavage and dictates nucleolar localization	Enhanced cell survival	60, 61
Akt2		Promotes tumorogenesis in human lung cancer cells	60, 61
MAPK/ERK	nPKC activation of MAPK/ERK signaling causes downregulation of NPM during differentiation	Differentiation of the cell	65
K-Ras	Interacts with GDP and GTP bound K-Ras at plasma membrane	Increased K-Ras stabilization and clustering leading to increased MAPK signaling	67
RelA	Relocalized to cytoplasm by nucleolar sequestered RelA	Decreased NF-kB transcriptional activity and increased apoptosis.	70, 73, 75
Bax	Colocalizes with Bax and p53 at mitochondrial membrane.	Induction of apoptosis	76-78
p53	Interferes with p53 mitochondrial localization	Inhibition of apoptosis	76-78