HOPS is an essential constituent of centrosome assembly.
Centrosomes direct microtubule organization during cell division. Aberrant number of centrosomes results from alteration of its components and leads to abnormal mitoses and chromosome instability. HOPS is a newly discovered protein isolated during liver regeneration, implicated in cell proliferation. Here, we provide evidence that HOPS is an integral constituent of centrosomes. HOPS is associated with classical markers of centrosomes and found in cytosolic complexes containing CRM-1, gamma-tubulin, eEF-1A and HSP70. These features suggest that HOPS is involved in centrosome assembly and maintenance. HOPS depletion generates supernumerary centrosomes, multinucleated cells and multipolar spindle formation leading to activation of p53 checkpoint and cell cycle arrest. The presence of HOPS in cytosolic complexes supports that centrosome proteins might be preassembled in the cytoplasm to then be rapidly recruited for centrosome duplication. Altogether these data show HOPS implication in the control of cell division. HOPS contribution appears relevant to understand genomic instability and centrosome amplification in cancer.
Pieroni
Stefania
S
Università degli Studi di Perugia, Dipartimento di Medicina Clinica e Sperimentale, Policlinico Monteluce, CEMIN, Perugia, Italy.
Della Fazia
Maria Agnese
MA
Castelli
Marilena
M
Piobbico
Danilo
D
Bartoli
Daniela
D
Brunacci
Cinzia
C
Bellet
Marina Maria
MM
Viola-Magni
Mariapia
M
Servillo
Giuseppe
G
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D042822:Genomic Instability / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides
D002352:Carrier Proteins; C531356:HOPS protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D009841:Oligonucleotides