Document Detail

Sgo1 as a "guardian spirit" for preventing colon tumorigenesis.
Jump to Full Text
MedLine Citation:
PMID:  22374668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Authors:
Robin M Ricke; Jan M van Deursen
Related Documents :
11886878 - C(4) photosynthesis: principles of co(2) concentration and prospects for its introducti...
15522508 - Multicellular life cycle of magnetotactic prokaryotes.
15180468 - T-cell-targeted biologicals for psoriasis.
22415928 - Human embryonic stem cells exhibit increased propensity to differentiate during the g1 ...
21490958 - Survival motor neuron protein regulates stem cell division, proliferation, and differen...
22898098 - A uremic toxin, 3-carboxy-4-methyl-5-propyl-2-furanpropionate induces cell damage to pr...
Publication Detail:
Type:  Comment; News    
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-29     Completed Date:  2012-09-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  649     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle Proteins / genetics*,  metabolism*
Centrosome / metabolism*
Chromosomal Instability*
Colonic Neoplasms / genetics*
Haploinsufficiency*
Grant Support
ID/Acronym/Agency:
R01 CA126828/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins
Comments/Corrections
Comment On:
Cell Cycle. 2012 Feb 1;11(3):479-88   [PMID:  22262168 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Cell Cycle
Journal ID (iso-abbrev): Cell Cycle
Journal ID (publisher-id): CC
ISSN: 1538-4101
ISSN: 1551-4005
Publisher: Landes Bioscience
Article Information
Download PDF
Copyright © 2012 Landes Bioscience
open-access:
Received Day: 29 Month: 12 Year: 2011
Accepted Day: 04 Month: 1 Year: 2012
Print publication date: Day: 15 Month: 2 Year: 2012
pmc-release publication date: Day: 15 Month: 2 Year: 2012
Volume: 11 Issue: 4
First Page: 649 Last Page: 649
PubMed Id: 22374668
ID: 3685617
Publisher Id: RickeCC11-4
DOI: 10.4161/cc.11.4.19360
Publisher Item Identifier: 19360

Sgo1 as a “guardian spirit” for preventing colon tumorigenesis
Robin M. Ricke1
Jan M. van Deursen12*
1Department of Pediatric and Adolescent Medicine; Mayo Clinic; Rochester, MN USA
2Department of Biochemistry and Molecular Biology; Mayo Clinic; Rochester, MN USA
*Correspondence to: Jan M. van Deursen; Email: vandeursen.jan@mayo.edu

High-fidelity chromosome segregation during both mitosis and meiosis is essential for the propagation and inheritance of stable genomes. Defects in these fundamental processes promote aberrant chromosome segregation, which, in the absence of cell death, produces aneuploid progeny. In somatic cells, aneuploidy is a putative cancer-promoting event. In germ cells, aneuploidy can reduce reproductive fertility and promote the accumulation of trisomies, such as those associated with Down, Patau or Edward syndromes. In order for maintenance of genomic integrity, cells have an elaborate network of proteins that function during mitosis and meiosis to ensure accurate chromosome segregation. One such proposed mitotic regulator is shugoshin. Whereas budding yeast and Drosophila contain a single shugoshin gene, fission yeast and mammals have two paralogs (Sgo1 and Sgo2). The exact role of the shugoshin family of proteins during mitosis and meiosis has been somewhat elusive. Several functions have been proposed for Sgo1, including protecting centromeric cohesion through associating with PP2A phosphatase,1 ensuring attachment error correction through chromosome passenger complex positioning,2 maintaining centriole cohesion3 and mediating kinetochore microtubule attachment by interacting directly with spindle microtubules.4 Like Sgo1, Sgo2 has also been similarly implicated in centromeric cohesion and attachment error correction, although under different cellular circumstances than Sgo1. On the other hand, Sgo2, but not Sgo1, is thought to function during mitosis through binding spindle microtubules through its association with astrin5 and through binding Mad2.6 Until now, the physiological consequences of deregulated Sgo1 had been unknown.

In a previous issue of Cell Cycle, Yamada and colleagues set out to assess the cellular and physiological consequences of reduced Sgo1 expression,7 since mouse Sgo1 encodes an essential gene. Importantly, which functions of Sgo1 are required for cell viability and whether this occurs at centromeres or centrosomes remains unknown. One hint that centromeric, mitotic Sgo1 may not be required for viability, however, comes from the observation that interphase Sgo1 is sufficient for the establishment of centromeric cohesion.8 This raises the question of what the function of mitotic Sgo1 is, in addition to whether and how it contributes to chromosome segregation. Consistent with the reported roles of Sgo1, mouse embryonic fibroblasts haploinsufficient for Sgo1 harbored both amplified centrosomes as well as chromosomes that were improperly attached to spindle microtubules. Whether the attachment defect was due to aberrant geometries from centrosome amplification,9 reduced correction of defective kinetochore microtubule interactions or precocious separation of sister chromatids is not known.

Because diminished Sgo1 expression had been previously linked to human colon neoplastic lesions, Yamada and colleagues challenged Sgo1 heterozygous mice with AOM, a carcinogen that generates DNA damage to initiate colon carcinogenesis. Importantly, mice heterozygous for Sgo1 harbored 5-fold more colon adenomas than wild-type mice at 12 weeks after completion of AOM treatment. Rather intriguingly, mice haploinsufficient for Sgo1 were actually more prone to cell death in the colonic mucosa compared with wild-type mice, at least in the initial phase of the experiment. This is a first demonstration of enhanced cell death following carcinogen challenge in a chromosomally unstable murine model. However, it remains an open question how enhanced cell death, although only immediately following carcinogen challenge, might alter the delicate balance regulating cell proliferation vs. cell death to influence tumor progression. This relationship could have significant implications in tumor etiology, progression and aggressiveness.

In summary, this study provides a causal link between diminished Sgo1 expression and induction of carcinogen-induced colon tumorigenesis. Additionally, these experiments raise a number of intriguing questions concerning the molecular mechanism for how Sgo1 contributes to high-fidelity chromosome segregation. The study of Sgo1 in mammals continues the line of investigation that began with the study of a single shugoshin gene in budding yeast and will likely lead to an increased understanding of the multiple layers of regulation necessary for proper chromosome segregation.


Notes

Previously published online: www.landesbioscience.com/journals/cc/article/19360

Notes


References
1. Xu Z,Ogawa H,Vagnarelli P,Bergmann JH,Hudson DF,Ruchaud S,et al. INCENP-aurora B interactions modulate kinase activity and chromosome passenger complex localizationJ Cell BiolYear: 20091876375310.1083/jcb.20090605319951914
2. Kawashima SA,Tsukahara T,Langegger M,Hauf S,Kitajima TS,Watanabe Y. Shugoshin enables tension-generating attachment of kinetochores by loading Aurora to centromeresGenes DevYear: 2007214203510.1101/gad.149730717322402
3. Schöckel L,Möckel M,Mayer B,Boos D,Stemmann O. Cleavage of cohesin rings coordinates the separation of centrioles and chromatidsNat Cell BiolYear: 2011139667210.1038/ncb228021743463
4. Salic A,Waters JC,Mitchison TJ. Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosisCellYear: 20041185677810.1016/j.cell.2004.08.01615339662
5. Dunsch AK,Linnane E,Barr FA,Gruneberg U. The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignmentJ Cell BiolYear: 20111929596810.1083/jcb.20100802321402792
6. Orth M,Mayer B,Rehm K,Rothweiler U,Heidmann D,Holak TA,et al. Shugoshin is a Mad1/Cdc20-like interactor of Mad2EMBO JYear: 20113028688010.1038/emboj.2011.18721666598
7. Yamada HY,Yao Y,Wang X,Zhang Y,Huang Y,Dai W,et al. Haploinsufficiency of SGO1 results in deregulated centrosome dynamics, enhanced chromosomal instability and colon tumorigenesisCell CycleYear: 2012 In press. 114798810.4161/cc.11.3.1899422262168
8. Perera D,Taylor SS. Sgo1 establishes the centromeric cohesion protection mechanism in G2 before subsequent Bub1-dependent recruitment in mitosisJ Cell SciYear: 2010123653910.1242/jcs.05950120124418
9. Ganem NJ,Godinho SA,Pellman D. A mechanism linking extra centrosomes to chromosomal instabilityNatureYear: 20094602788210.1038/nature0813619506557

Article Categories:
  • Cell Cycle News & Views


Previous Document:  TRIM8 and p53: Making the right decision.
Next Document:  Sgo1 as a guardian of chromosome stability.