Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication.
BACKGROUND
Nucleolin is a major component of the nucleolus, but is also found in other cell compartments. This protein is involved in various aspects of ribosome biogenesis from transcription regulation to the assembly of pre-ribosomal particles; however, many reports suggest that it could also play an important role in non nucleolar functions. To explore nucleolin function in cell proliferation and cell cycle regulation we used siRNA to down regulate the expression of nucleolin.


RESULTS
We found that, in addition to the expected effects on pre-ribosomal RNA accumulation and nucleolar structure, the absence of nucleolin results in a cell growth arrest, accumulation in G2, and an increase of apoptosis. Numerous nuclear alterations, including the presence of micronuclei, multiple nuclei or large nuclei are also observed. In addition, a large number of mitotic cells showed a defect in the control of centrosome duplication, as indicated by the presence of more than 2 centrosomes per cell associated with a multipolar spindle structure in the absence of nucleolin. This phenotype is very similar to that obtained with the inactivation of another nucleolar protein, B23.


CONCLUSIONS
Our findings uncovered a new role for nucleolin in cell division, and highlight the importance of nucleolar proteins for centrosome duplication.
Ugrinova
Iva
I
Laboratory Joliot-Curie, CNRS USR 3010, University of Lyon, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, Lyon, France. ugryiva2003@yahoo.com
Monier
Karine
K
Ivaldi
Corinne
C
Thiry
Marc
M
Storck
Sébastien
S
Mongelard
Fabien
F
Bouvet
Philippe
P
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002466:Cell Nucleolus / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus; D000097796:Nucleolin
D010750:Phosphoproteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097796:Nucleolin
J Biol Chem. 1985 Jul 5;260(13):8050-5
4008489
J Cell Sci. 2007 Jun 15;120(Pt 12):2091-105
17535846
Proc Natl Acad Sci U S A. 1987 Oct;84(19):6770-4
3477808
EMBO J. 1988 Jun;7(6):1621-6
3139405
Exp Cell Res. 1988 Oct;178(2):264-72
3169130
Cell. 1989 Feb 10;56(3):379-90
2914325
Biochemistry. 1989 Nov 28;28(24):9495-501
2482073
Bioessays. 1990 Jan;12(1):14-21
2181998
Biochem Biophys Res Commun. 1991 Oct 31;180(2):716-23
1953744
Prostate. 1994;24(2):101-6
8309845
Exp Cell Res. 1994 Oct;214(2):465-72
7523152
FEBS Lett. 1983 May 8;155(2):218-22
6852233
Nucleic Acids Res. 1984 Apr 11;12(7):3025-35
6562463
J Histochem Cytochem. 1994 Nov;42(11):1513-7
7930534
Cell Prolif. 1995 Jun;28(6):329-36
7626687
Exp Cell Res. 1995 Jul;219(1):276-82
7628543
J Histochem Cytochem. 1995 Sep;43(9):887-93
7642962
Lab Invest. 1995 Oct;73(4):497-502
7474921
Eur J Biochem. 1996 Apr 1;237(1):153-8
8620867
J Mol Biol. 1996 Jul 5;260(1):34-53
8676391
J Biol Chem. 1996 Oct 4;271(40):24781-7
8798749
Chromosoma. 1997 Jun;105(7-8):496-505
9211977
Cytometry. 1997 Jun 1;28(2):147-56
9181305
Chromosoma. 1997 Nov;106(6):348-60
9362543
EMBO J. 1998 Mar 2;17(5):1476-86
9482744
J Biol Chem. 1998 Jul 24;273(30):19025-9
9668083
Nucleic Acids Res. 1998 Oct 1;26(19):4508-15
9742256
J Cell Sci. 1999 Mar;112 ( Pt 6):761-72
10036227
Protein Sci. 1999 Apr;8(4):905-12
10211837
J Biol Chem. 1999 Sep 10;274(37):26369-77
10473594
Cancer Lett. 1999 Sep 20;144(1):45-54
10503877
Histochem Cell Biol. 2005 Mar;123(3):203-16
15742198
Mol Cell. 2005 Jul 1;19(1):77-87
15989966
Nat Cell Biol. 2005 Aug;7(8):823-30
16041368
Nature. 2005 Sep 1;437(7055):147-53
16007073
Cell Cycle. 2005 Aug;4(8):1036-8
16205120
Cell. 2005 Oct 7;123(1):49-63
16213212
Cancer Lett. 2005 Dec 8;230(1):6-19
16253756
FEBS Lett. 2005 Dec 5;579(29):6621-34
16297385
J Biol Chem. 2000 Jun 23;275(25):18845-50
10858445
Cell. 2000 Sep 29;103(1):127-40
11051553
EMBO J. 2000 Dec 15;19(24):6870-81
11118222
FEBS Lett. 2001 Oct 12;506(3):272-6
11602260
J Biol Chem. 2001 Nov 16;276(46):43221-30
11555643
J Biol Chem. 2002 Mar 22;277(12):10209-19
11773064
Oncogene. 2002 Sep 9;21(40):6170-4
12214246
Chromosoma. 2003 Mar;111(6):399-407
12644954
EMBO J. 2003 Nov 17;22(22):6068-77
14609953
Nature. 2003 Dec 4;426(6966):570-4
14654843
Mass Spectrom Rev. 2006 Mar-Apr;25(2):215-34
16211575
EMBO J. 2006 Apr 19;25(8):1669-79
16601700
Mol Cell Biol. 2006 May;26(10):3798-809
16648475
Cell Res. 2006 Jun;16(6):530-8
16775624
Nat Rev Cancer. 2006 Jul;6(7):493-505
16794633
Mol Cell Biol. 2006 Dec;26(23):9016-34
17015463
Oncogene. 2006 Nov 23;25(55):7274-88
16751805
Bioessays. 2007 Jan;29(1):49-59
17187372
Mol Cell Biol. 2007 Feb;27(3):937-48
17130237
Trends Cell Biol. 2007 Feb;17(2):80-6
17157503
Biol Cell. 1985;54(1):57-64
2411316