Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0033036 (
APC
)
10,214
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The G2 DNA damage checkpoint is one of the most important mechanisms controlling G2-mitosis transition. The kinase Greatwall (MASTL in human) promotes normal G2-mitosis transition by inhibiting PP2A via ARPP19 and
ENSA
. In this study, we demonstrate that MASTL is critical for maintaining genome integrity after DNA damage. Although MASTL did not affect the activation of DNA damage responses and subsequent repair, it determined the timing of entry into mitosis and the subsequent fate of the recovering cells. Constitutively active MASTL promoted dephosphorylation of CDK1(Tyr15) and accelerated mitotic entry after DNA damage. Conversely, downregulation of MASTL or ARPP19/
ENSA
delayed mitotic entry. Remarkably,
APC
/C was activated precociously, resulting in the damaged cells progressing from G2 directly to G1 and skipping mitosis all together. Collectively, these results established that precise control of MASTL is essential to couple DNA damage to mitosis through the rate of mitotic entry and
APC
/C activation.
...
PMID:MASTL(Greatwall) regulates DNA damage responses by coordinating mitotic entry after checkpoint recovery and APC/C activation. 2692 77
Here, we will review the evidence showing that mitotic exit is initiated by regulated proteolysis and then driven by the PPP family of phosphoserine/threonine phosphatases. Rapid
APC
/C
CDC
20
and ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid separation, the first step of mitotic exit. Because proteolysis of Aurora and Polo family kinases dependent on
APC
/C
CDH
1
is relatively slow, this creates a new regulatory state, anaphase, different to G2 and M-phase. We will discuss how the CDK1-counteracting phosphatases PP1 and PP2A-B55, together with Aurora and Polo kinases, contribute to the temporal regulation and order of events in the different stages of mitotic exit from anaphase to cytokinesis. For PP2A-B55, these timing properties are created by the
ENSA
-dependent inhibitory pathway and differential recognition of phosphoserine and phosphothreonine. Finally, we will discuss how Aurora B and PP2A-B56 are needed for the spatial regulation of anaphase spindle formation and how
APC
/C-dependent destruction of PLK1 acts as a timer for abscission, the final event of cytokinesis.
...
PMID:Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A. 3149 26
