|
Ovi nenormalni slučajevi i mogu uzrokovati tumore, među njima i maligne. Takve abnormalnosti se, međutim, često prestražuju u histopatološkoj analizi i procjeni maligniteta tumorske mase.
[[CLIP1|CLIP170]] pokazuje lokalizaciju krajeva mikrotubula u ''HeLa'' tumosrskim ćelijama<ref>{{cite journal |author=J.E. Rickard, T.E. Kreis|title=Identification of a novel nucleotide-sensitive microtubule-binding protein in HeLa cells|journal=J Cell Biol|year=1990|volume=110|pages=1623–1633 |doi=10.1083/jcb.110.5.1623 |pmid=1970824 |issue=5 |pmc=2200191}}</ref> and to accumulate in kinetochores during [[prometaphase]].<ref>{{cite journal |author=D. Dujardin, U.I. Wacker, A. Moreau, T.A. Schroer, J.E. Rickard, J.R. DeMey|title=Evidence for a role of CLIP-170 in the establishment of metaphase chromosome alignment|journal=J Cell Biol|year=1998|volume=141|pages=849–862 |doi=10.1083/jcb.141.4.849 |pmid=9585405 |issue=4 |pmc=2132766}}</ref>
n and attainment of [[Spindle_checkpoint#Chromosome_segregation|bipolarity]]. The [[kinesin]]-13 superfamily of MAPs contains a class of plus-end-directed motor proteins with associated microtubule depolymerization activity including the well-studied mammalian [[MCAK]] and ''Xenopus'' [[XKCM1]]. MCAK localizes to the growing tips of microtubules at kinetochores where it can trigger catastrophe in direct competition with stabilizing +TIP activity.<ref name="M.E. Tanenbaum, R.H. Medema, A. Akhmanova 2011 80–87">{{cite journal |author=M.E. Tanenbaum, R.H. Medema, A. Akhmanova|title=Regulation of localization and activity of the microtubule depolymerase MCAK|journal=Bioarchitecture|year=2011|volume=1|pages=80–87 |doi=10.4161/bioa.1.2.15807 |pmid=21866268 |issue=2 |pmc=3158623}}</ref> These proteins harness the energy of [[ATP hydrolysis]] to induce destabilizing conformational changes in protofilament structure that cause kinesin release and microtubule depolymerization.<ref>{{cite journal |author=H. Niederstrasser, H. Salehi-Had, E.C. Gan, C. Walczak, E. Nogales|title=XKCM1 acts on a single protofilament and requires the C terminus of tubulin|journal=J Mol Biol|year=2002|volume=316|pages=817–828 |doi=10.1006/jmbi.2001.5360 |pmid=11866534 |issue=3}}</ref> Loss of their activity results in numerous mitotic defects.<ref name="M.E. Tanenbaum, R.H. Medema, A. Akhmanova 2011 80–87"/> Additional microtubule destabilizing proteins include Op18/stathmin and katanin which have roles in remodeling the mitotic spindle as well as promoting chromosome segregation during anaphase.<ref name="H. Maiato, P Sampaio, C.E. Sunkel 2004 53–153">{{cite journal |author=H. Maiato, P Sampaio, C.E. Sunkel|title=Microtubule-associated proteins and their essential roles during mitosis|journal=Int Rev Cytol|year=2004|volume=241|pages=53–153 |doi=10.1016/S0074-7696(04)41002-X |pmid=15548419 }}</ref>
The activities of these MAPs are carefully regulated to maintain proper microtubule dynamics during spindle assembly, with many of these proteins serving as [[Aurora kinase|Aurora]] and [[Polo-like kinase]] substrates.<ref name="H. Maiato, P Sampaio, C.E. Sunkel 2004 53–153"/> As a testament to this, proper microtubule dynamics can be recapitulated in ''Xenopus'' egg extract by the balanced activity of the stabilizing factor [[XMAP215]] and the destabilizing factor XKCM1.<ref>{{cite journal |author=R. Tournebize, A. Popov, K. Kinoshita, A.J. Ashford, et al.|title=Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts|journal=Nat Cell Biol|year=2000|volume=2|pages=13–19|pmid=10620801|doi=10.1038/71330}}</ref>
== Reference ==
|
