Abstract
Pocket proteins negatively regulate transcription of E2F-dependent genes and progression through the G0/G1 transition and the cell cycle restriction point in G1. Pocket protein repressor activities are inactivated via phosphorylation at multiple Pro-directed Ser/Thr sites by the coordinated action of G1 and G1/S cyclin-dependent kinases. These phosphorylations are reversed by the action of two families of Ser/Thr phosphatases: PP1, which has been implicated in abrupt dephosphorylation of retinoblastoma protein (pRB) in mitosis, and PP2A, which plays a role in an equilibrium that counteracts cyclin-dependent kinase (CDK) action throughout the cell cycle. However, the identity of the trimeric PP2A holoenzyme(s) functioning in this process is unknown. Here we report the identification of a PP2A trimeric holoenzyme containing B55α, which plays a major role in restricting the phosphorylation state of p107 and inducing its activation in human cells. Our data also suggest targeted selectivity in the interaction of pocket proteins with distinct PP2A holoenzymes, which is likely necessary for simultaneous pocket protein activation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 29863-29873 |
| Number of pages | 11 |
| Journal | Journal of Biological Chemistry |
| Volume | 285 |
| Issue number | 39 |
| DOIs | |
| State | Published - Sep 24 2010 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Medicine(all)
Cite this
B55α PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation. / Jayadeva, Girish; Kurimchak, Alison; Garriga, Judit; Sotillo, Elena; Davis, Anthony J.; Haines, Dale S.; Mumby, Marc; Graña, Xavier.
In: Journal of Biological Chemistry, Vol. 285, No. 39, 24.09.2010, p. 29863-29873.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - B55α PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation
AU - Jayadeva, Girish
AU - Kurimchak, Alison
AU - Garriga, Judit
AU - Sotillo, Elena
AU - Davis, Anthony J.
AU - Haines, Dale S.
AU - Mumby, Marc
AU - Graña, Xavier
PY - 2010/9/24
Y1 - 2010/9/24
N2 - Pocket proteins negatively regulate transcription of E2F-dependent genes and progression through the G0/G1 transition and the cell cycle restriction point in G1. Pocket protein repressor activities are inactivated via phosphorylation at multiple Pro-directed Ser/Thr sites by the coordinated action of G1 and G1/S cyclin-dependent kinases. These phosphorylations are reversed by the action of two families of Ser/Thr phosphatases: PP1, which has been implicated in abrupt dephosphorylation of retinoblastoma protein (pRB) in mitosis, and PP2A, which plays a role in an equilibrium that counteracts cyclin-dependent kinase (CDK) action throughout the cell cycle. However, the identity of the trimeric PP2A holoenzyme(s) functioning in this process is unknown. Here we report the identification of a PP2A trimeric holoenzyme containing B55α, which plays a major role in restricting the phosphorylation state of p107 and inducing its activation in human cells. Our data also suggest targeted selectivity in the interaction of pocket proteins with distinct PP2A holoenzymes, which is likely necessary for simultaneous pocket protein activation.
AB - Pocket proteins negatively regulate transcription of E2F-dependent genes and progression through the G0/G1 transition and the cell cycle restriction point in G1. Pocket protein repressor activities are inactivated via phosphorylation at multiple Pro-directed Ser/Thr sites by the coordinated action of G1 and G1/S cyclin-dependent kinases. These phosphorylations are reversed by the action of two families of Ser/Thr phosphatases: PP1, which has been implicated in abrupt dephosphorylation of retinoblastoma protein (pRB) in mitosis, and PP2A, which plays a role in an equilibrium that counteracts cyclin-dependent kinase (CDK) action throughout the cell cycle. However, the identity of the trimeric PP2A holoenzyme(s) functioning in this process is unknown. Here we report the identification of a PP2A trimeric holoenzyme containing B55α, which plays a major role in restricting the phosphorylation state of p107 and inducing its activation in human cells. Our data also suggest targeted selectivity in the interaction of pocket proteins with distinct PP2A holoenzymes, which is likely necessary for simultaneous pocket protein activation.
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UR - http://www.scopus.com/inward/citedby.url?scp=77956901785&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110.162354
DO - 10.1074/jbc.M110.162354
M3 - Article
C2 - 20663872
AN - SCOPUS:77956901785
VL - 285
SP - 29863
EP - 29873
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 39
ER -