Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19 Arf network.
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 p19(Arf), 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 p19(Arf), 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 p19(Arf), providing new mechanistic insight into how NPM and p19(Arf) will oppose tumor cell proliferation.
Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
M
M
Castelli
S
S
Pieroni
C
C
Brunacci
D
D
Piobbico
D
D
Bartoli
M M
MM
Bellet
E
E
Colombo
P G
PG
Pelicci
M A
MA
Della Fazia
G
G
Servillo
D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D021381:Protein Transport
D002352:Carrier Proteins; C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; C531356:HOPS protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin