Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Aug 15;9(16):3194-201.
doi: 10.4161/cc.9.16.12619. Epub 2010 Aug 9.

The fate of metaphase kinetochores is weighed in the balance of SUMOylation during S phase

Debaditya Mukhopadhyay  1 , Mary Dasso
Affiliations
Review

The fate of metaphase kinetochores is weighed in the balance of SUMOylation during S phase

Debaditya Mukhopadhyay et al. Cell Cycle. .

Abstract

Genetic evidence suggests that conjugation of Small Ubiquitin-like Modifier proteins (SUMOs) plays an important role in kinetochore function, although the mechanism underlying these observations are poorly defined. We found that depletion of the SUMO protease SENP6 from HeLa cells causes chromosome misalignment, prolonged mitotic arrest and chromosome missegregation. Many inner kinetochore proteins (IKPs) were mis-localized in SENP6-depleted cells. This gross mislocalization of IKPs is due to proteolytic degradation of CENP-I and CENP-H via the SUMO targeted Ubiquitin Ligase (STUbL) pathway. Our findings show that SENP6 is a key regulator of inner kinetochore assembly that antagonizes the cellular STUbL pathway to protect IKPs from degradation during S phase. Here, we will briefly review the implications of our findings and present new data on how SUMOylation during S phase can control chromosome alignment in the subsequent metaphase.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of STUbL degradation pathway. Enzymes of the SUMO conjugation pathway are indicated with s (sE1, sE2, sE3), while enzymes involved in ubiquitin conjugation are indicated with u (uE1, uE2) or as STUbL (E3 enzyme). SENPs are SUMO deconjugating enzymes, while DUBs are ubiquitin deconjugating enzymes.
Figure 2
Figure 2
Schematic representation of the genetic and molecular interactions of the different kinetochore proteins. Filled arrows indicate complete dependence and broken arrows indicate partial dependence.
Figure 3
Figure 3
Plk localization is indirectly disrupted after SENP6 depletion. we treated HeLa cells with Control, SENP-6, CENP-I and CENP-O siRNA for 48 hours, and simultaneously synchronized the cells using a double thymidine block protocol, as described. Ten hours after release from the second thymidine block, the cells were preextracted, fixed in 4% paraformaldehyde, and stained for centrosomes (Centrin 2 antisera; red) and Plk1 (green) Images (i–iv) represents control, SENP-6, CENP-I and CENP-O knockdown respectively. SENP6 depletion in HeLa cells resulted in loss of punctuate Plk1 signal at the metaphase plate (i and ii), which we have confirmed as centromeric Plk1 (data not shown). Similar loss of Plk1 was also observed in case of CENP-I and CENP-O knockdown (iii and iv). The arrows indicate cytoplasmic Plk1 aggregates.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Geiss-Friedlander R, Melchior F. Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol. 2007;8:947–956. - PubMed
    1. Johnson ES. Protein modification by SUMO. Annu Rev Biochem. 2004;73:355–382. - PubMed
    1. Hay RT. SUMO-specific proteases: a twist in the tail. Trends Cell Biol. 2007;17:370–376. - PubMed
    1. Mukhopadhyay D, Dasso M. Modification in reverse: the SUMO proteases. Trends Biochem Sci. 2007;32:286–295. - PubMed
    1. Li SJ, Hochstrasser M. The yeast ULP2 (SMT4) gene encodes a novel protease specific for the ubiquitin-like Smt3 protein. Mol Cell Biol. 2000;20:2367–2377. - PMC - PubMed

Substances