Abstract
Nucleophosmin (NPM), a ubiquitously and abundantly expressed protein, occurs in the nucleolus, shuttling between the nucleoplasm and cytoplasm. The NPM gene is mutated in almost 30% of human acute myeloid leukemia cells. NPM interacts with p53 and p19Arf, directs localization of p19 Arf in the nucleolus and protects the latter from degradation. Hepatocyte odd protein shuttling (HOPS) is also a ubiquitously expressed protein that moves between the nucleus and cytoplasm. Within the nucleus of resting cells, HOPS overexpression causes cell cycle arrest in G0/G1. HOPS knockdown causes centrosome hyperamplification leading to multinucleated cells and the formation of micronuclei. We demonstrate a direct interaction of HOPS with NPM and p19Arf, resulting in a functionally active trimeric complex. NPM appeared to regulate HOPS half-life, which, in turn, stabilized p19 Arf and controlled its localization in the nucleolus. These findings suggest that HOPS acts as a functional bridge in the interaction between NPM and p19Arf, providing new mechanistic insight into how NPM and p19 Arf will oppose tumor cell proliferation.
| Original language | English |
|---|---|
| Pages (from-to) | 3350-3358 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 32 |
| Issue number | 28 |
| DOIs | |
| Publication status | Published - Jul 11 2013 |
Fingerprint
Keywords
- Hepatocyte odd protein shuttling (HOPS)
- Nucleophosmin (NPM)
- p19
- Tmub1
- Tumor suppressor gene
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19Arf network. / Castelli, M.; Pieroni, S.; Brunacci, C.; Piobbico, D.; Bartoli, D.; Bellet, M. M.; Colombo, E.; Pelicci, P. G.; Della Fazia, M. A.; Servillo, G.
In: Oncogene, Vol. 32, No. 28, 11.07.2013, p. 3350-3358.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19Arf network
AU - Castelli, M.
AU - Pieroni, S.
AU - Brunacci, C.
AU - Piobbico, D.
AU - Bartoli, D.
AU - Bellet, M. M.
AU - Colombo, E.
AU - Pelicci, P. G.
AU - Della Fazia, M. A.
AU - Servillo, G.
PY - 2013/7/11
Y1 - 2013/7/11
N2 - Nucleophosmin (NPM), a ubiquitously and abundantly expressed protein, occurs in the nucleolus, shuttling between the nucleoplasm and cytoplasm. The NPM gene is mutated in almost 30% of human acute myeloid leukemia cells. NPM interacts with p53 and p19Arf, directs localization of p19 Arf in the nucleolus and protects the latter from degradation. Hepatocyte odd protein shuttling (HOPS) is also a ubiquitously expressed protein that moves between the nucleus and cytoplasm. Within the nucleus of resting cells, HOPS overexpression causes cell cycle arrest in G0/G1. HOPS knockdown causes centrosome hyperamplification leading to multinucleated cells and the formation of micronuclei. We demonstrate a direct interaction of HOPS with NPM and p19Arf, resulting in a functionally active trimeric complex. NPM appeared to regulate HOPS half-life, which, in turn, stabilized p19 Arf and controlled its localization in the nucleolus. These findings suggest that HOPS acts as a functional bridge in the interaction between NPM and p19Arf, providing new mechanistic insight into how NPM and p19 Arf will oppose tumor cell proliferation.
AB - Nucleophosmin (NPM), a ubiquitously and abundantly expressed protein, occurs in the nucleolus, shuttling between the nucleoplasm and cytoplasm. The NPM gene is mutated in almost 30% of human acute myeloid leukemia cells. NPM interacts with p53 and p19Arf, directs localization of p19 Arf in the nucleolus and protects the latter from degradation. Hepatocyte odd protein shuttling (HOPS) is also a ubiquitously expressed protein that moves between the nucleus and cytoplasm. Within the nucleus of resting cells, HOPS overexpression causes cell cycle arrest in G0/G1. HOPS knockdown causes centrosome hyperamplification leading to multinucleated cells and the formation of micronuclei. We demonstrate a direct interaction of HOPS with NPM and p19Arf, resulting in a functionally active trimeric complex. NPM appeared to regulate HOPS half-life, which, in turn, stabilized p19 Arf and controlled its localization in the nucleolus. These findings suggest that HOPS acts as a functional bridge in the interaction between NPM and p19Arf, providing new mechanistic insight into how NPM and p19 Arf will oppose tumor cell proliferation.
KW - Hepatocyte odd protein shuttling (HOPS)
KW - Nucleophosmin (NPM)
KW - p19
KW - Tmub1
KW - Tumor suppressor gene
UR - http://www.scopus.com/inward/record.url?scp=84880320748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880320748&partnerID=8YFLogxK
U2 - 10.1038/onc.2012.353
DO - 10.1038/onc.2012.353
M3 - Article
C2 - 22890319
AN - SCOPUS:84880320748
VL - 32
SP - 3350
EP - 3358
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 28
ER -