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Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint

Campaner, Stefano ; Kaldis, Philipp LU ; Izraeli, Shai and Kirsch, Ilan R. (2005) In Molecular and Cellular Biology 25(15). p.6660-6672
Abstract

SIL is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations. We now show that the Sil protein is hyperphosphorylated during mitosis or in cells blocked at prometaphase by microtubule inhibitors. Cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis. Point mutation of the seven (S/T)P sites between amino acids 567 and 760 reduces mitotic phosphorylation of Sil, Pin1 binding, and spindle checkpoint duration. When a phosphorylation site mutant Sil is stably expressed, the duration of the spindle checkpoint is shortened in cells challenged with taxol or nocodazole, and the cells revert to a G2-like... (More)

SIL is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations. We now show that the Sil protein is hyperphosphorylated during mitosis or in cells blocked at prometaphase by microtubule inhibitors. Cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis. Point mutation of the seven (S/T)P sites between amino acids 567 and 760 reduces mitotic phosphorylation of Sil, Pin1 binding, and spindle checkpoint duration. When a phosphorylation site mutant Sil is stably expressed, the duration of the spindle checkpoint is shortened in cells challenged with taxol or nocodazole, and the cells revert to a G2-like state. This event is associated with the downregulation of the kinase activity of the Cdc2/cyclin B1 complex and the dephosphorylation of the threonine 161 on the Cdc2 subunit. Sil downregulation by plasmid-mediated RNA interference limited the ability of cells to activate the spindle checkpoint and correlated with a reduction of Cdc2/cyclin B1 activity and phosphorylation on T161 on the Cdc2 subunit. These data suggest that a critical region of Sil is required to mediate the presentation of Cdc2 activity during spindle checkpoint arrest.

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author
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publishing date
type
Contribution to journal
publication status
published
in
Molecular and Cellular Biology
volume
25
issue
15
pages
6660 - 6672
publisher
American Society for Microbiology
external identifiers
  • pmid:16024801
  • scopus:22544461011
ISSN
0270-7306
DOI
10.1128/MCB.25.15.6660-6672.2005
language
English
LU publication?
no
id
e9b4e96d-7e3b-4aec-8093-785a088646ea
date added to LUP
2019-09-18 14:26:52
date last changed
2021-02-17 07:37:13
@article{e9b4e96d-7e3b-4aec-8093-785a088646ea,
  abstract     = {<p>SIL is an immediate-early gene that is essential for embryonic development and is implicated in T-cell leukemia-associated translocations. We now show that the Sil protein is hyperphosphorylated during mitosis or in cells blocked at prometaphase by microtubule inhibitors. Cell cycle-dependent phosphorylation of Sil is required for its interaction with Pin1, a regulator of mitosis. Point mutation of the seven (S/T)P sites between amino acids 567 and 760 reduces mitotic phosphorylation of Sil, Pin1 binding, and spindle checkpoint duration. When a phosphorylation site mutant Sil is stably expressed, the duration of the spindle checkpoint is shortened in cells challenged with taxol or nocodazole, and the cells revert to a G<sub>2</sub>-like state. This event is associated with the downregulation of the kinase activity of the Cdc2/cyclin B1 complex and the dephosphorylation of the threonine 161 on the Cdc2 subunit. Sil downregulation by plasmid-mediated RNA interference limited the ability of cells to activate the spindle checkpoint and correlated with a reduction of Cdc2/cyclin B1 activity and phosphorylation on T161 on the Cdc2 subunit. These data suggest that a critical region of Sil is required to mediate the presentation of Cdc2 activity during spindle checkpoint arrest.</p>},
  author       = {Campaner, Stefano and Kaldis, Philipp and Izraeli, Shai and Kirsch, Ilan R.},
  issn         = {0270-7306},
  language     = {eng},
  month        = {08},
  number       = {15},
  pages        = {6660--6672},
  publisher    = {American Society for Microbiology},
  series       = {Molecular and Cellular Biology},
  title        = {Sil phosphorylation in a Pin1 binding domain affects the duration of the spindle checkpoint},
  url          = {http://dx.doi.org/10.1128/MCB.25.15.6660-6672.2005},
  doi          = {10.1128/MCB.25.15.6660-6672.2005},
  volume       = {25},
  year         = {2005},
}