Biology Reference
In-Depth Information
resulting in massive architectural changes to the cell, such as centrosome matu-
ration and separation, chromosome condensation and nuclear envelope break-
down. For example, CDK1-mediated phosphorylation of motor proteins, such as
the kinesin-like protein Eg5, regulates centrosome separation and transformation
into the bipolar spindle (Blangy et al.
1995
). Nuclear CDK1-cyclin B phosphor-
ylates other proteins, such as condensin, which results in chromosome conden-
sation (Kimura et al.
1998
; Kimura and Hirano
1997
) and lamins, which cause
nuclear membrane breakdown (Peter et al.
1990
). However, CDK1 is not solely
responsible for driving mitosis, as other kinases, such as the polo-like and aurora
kinase families, also play key roles in regulating mitotic progression (Glover et al.
1998
; Eyers and Maller
2003
).
11.3 Conclusions
Centrosome replication is largely controlled by the activity of CDK2 in complex
with cyclins E/A. Three CDK2 centrosome substrates have been identified to date
and together, these are involved in all stages of centrosome replication—initiation,
elongation and separation. In addition, phosphorylation of all three CDK substrates
appears to control their local protein concentration at the centrosome. Dissociation
of NPM and CP110 from the centrosome cause a decrease and protection of Mps1
from degradation causes an increase in centrosomal protein levels. Misregulation
of any one of these can cause centrosome re-replication, resulting in abnormal
centrosome numbers and abnormal mitotic spindles. Such defects are found in
most human cancers and may contribute to tumourigenesis.
References
Russell P, Nurse P (1986) Cell 45:781-782
Lee MG, Nurse P (1987) Nature 327:31-35
Malumbres M, Barbacid M (2005) Trends Biochem Sci 30:630-641
Bourne Y, Watson MH, Hickey MJ, Holmes W, Rocque W, Reed SI, Tainer JA (1996) Cell
84:863-874
De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (1993) Nature 363:595-602
Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T (1983) Cell 33:389-396
Satyanarayana A, Kaldis P (2009) Oncogene 28:2925-2939
Morgan DO (1995) Nature 374:131-134
King RW, Deshaies RJ, Peters JM, Kirschner MW (1996) Science 274:1652-1659
Booher RN, Alfa CE, Hyams JS, Beach DH (1989) Cell 58:485-497
Clurman BE, Sheaff RJ, Thress K, Groudine M, Roberts JM (1996) Genes Dev 10:1979-1990
Won KA, Reed SI (1996) EMBO J 15:4182-4193
Hunt T, Luca FC, Ruderman JV (1992) J Cell Biol 116:707-724
Pines J, Hunter T (1990) Nature 346:760-763
Peeper DS, Parker LL, Ewen ME, Toebes M, Hall FL, Xu M, Zantema A, van der Eb AJ,
Piwnica-Worms H (1993) EMBO J 12:1947-1954
