Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Smurf2 as a novel mitotic regulator: From the spindle assembly
checkpoint to tumorigenesis
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| Creator |
Osmundson, Evan C
Ray, Dipankar Moore, Finola E Kiyokawa, Hiroaki |
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| Subject |
Cell Biology & Physiology
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| Description |
The execution of the mitotic program with high fidelity is dependent upon precise spatiotemporal
regulation of posttranslational protein modifications. For example, the timely polyubiquitination of
critical mitotic regulators by Anaphase Promoting Complex/Cyclosome (APC/C) is essential for
the metaphase to anaphase transition and mitotic exit. The spindle assembly checkpoint prevents
unscheduled activity of APC/C-Cdc20 in early mitosis, allowing bipolar attachment of kinetochores
to mitotic spindle and facilitating equal segregation of sister chromatids. The critical effector of the
spindle checkpoint, Mitotic arrest deficient 2 (Mad2), is recruited to unattached kinetochores
forming a complex with other regulatory proteins to efficiently and cooperatively inhibit APC/CCdc20.
A weakened and/or dysfunctional spindle checkpoint has been linked to the development
of genomic instability in both cell culture and animal models, and evidence suggests that aberrant
regulation of the spindle checkpoint plays a critical role in human carcinogenesis. Recent studies
have illuminated a network of both degradative and non-degradative ubiquitination events that
regulate the metaphase to anaphase transition and mitotic exit. Within this context, our recent
work showed that the HECT (Homologous to E6-AP C-terminus)-family E3 ligase Smurf2 (Smad
specific ubiquitin regulatory factor 2), known as a negative regulator of transforming growth factorbeta
(TGF-β) signaling, is required for a functional spindle checkpoint by promoting the functional
localization and stability of Mad2. Here we discuss putative models explaining the role of Smurf2 as
a new regulator in the spindle checkpoint. The dynamic mitotic localization of Smurf2 to the
centrosome and other critical mitotic structures provides implications about mitotic checkpoint
control dependent on various ubiquitination events. Finally, deregulated Smurf2 activity may
contribute to carcinogenesis by perturbed mitotic control.
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| Date |
2009
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/138/1/CELL_DIVISION%2C__4_(14)%2C2009[48].pdf
Osmundson, Evan C and Ray, Dipankar and Moore, Finola E and Kiyokawa, Hiroaki (2009) Smurf2 as a novel mitotic regulator: From the spindle assembly checkpoint to tumorigenesis. Cell Division, 4 (14). |
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| Relation |
http://dx.doi.org/10.1186/1747-1028-4-14
http://www.eprints.iicb.res.in/138/ |
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