The centrosome protein NEDD1 as a potential pharmacological target to induce cell cycle arrest.
BACKGROUND
NEDD1 is a protein that binds to the gamma-tubulin ring complex, a multiprotein complex at the centrosome and at the mitotic spindle that mediates the nucleation of microtubules.


RESULTS
We show that NEDD1 is expressed at comparable levels in a variety of tumor-derived cell lines and untransformed cells. We demonstrate that silencing of NEDD1 expression by treatment with siRNA has differential effects on cells, depending on their status of p53 expression: p53-positive cells arrest in G1, whereas p53-negative cells arrest in mitosis with predominantly aberrant monopolar spindles. However, both p53-positive and -negative cells arrest in mitosis if treated with low doses of siRNA against NEDD1 combined with low doses of the inhibitor BI2536 against the mitotic kinase Plk1. Simultaneous reduction of NEDD1 levels and inhibition of Plk1 act in a synergistic manner, by potentiating the anti-mitotic activity of each treatment.


CONCLUSIONS
We propose that NEDD1 may be a promising target for controlling cell proliferation, in particular if targeted in combination with Plk1 inhibitors.
Tillement
Vanessa
V
Centre National de la Recherche Scientifique - Pierre Fabre, UMR 2587, 3 rue des Satellites, 31400 Toulouse, France. vanessa.tillement@istmt.cnrs.fr
Haren
Laurence
L
Roullet
Nicolas
N
Etievant
Chantal
C
Merdes
Andreas
A
D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018385:Centrosome / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000069476:Linagliptin; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D011687:Purines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D000069476:Linagliptin; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011687:Purines; D011799:Quinazolines; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D000097869:Polo-Like Kinase 1; C509189:NEDD1 protein, human