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.
(Less)
- author
- Campaner, Stefano
; Kaldis, Philipp
LU
; Izraeli, Shai
and Kirsch, Ilan R.
- publishing date
- 2005-08-01
- 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
-
- scopus:22544461011
- pmid:16024801
- 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
- 2024-08-07 06:39:56
@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}},
}