Cyclin A/Cdk2 complexes regulate activation of Cdk1 and Cdc25 phosphatases in human cells

Mitra, Jayashree; Enders, Greg H.

doi:10.1038/sj.onc.1207446

Cited by 78 publications

(86 citation statements)

References 42 publications

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“…In agreement with these reports, the present study demonstrates that inhibition of G 2 phase cyclin A/cdk2 delays the cdc25-dependent activation (Mitra and Enders, 2004;Fung et al, 2007), and nuclear translocation (Gong et al, 2007) of cyclin B/cdk1. The accumulated evidence now presents a convincing case that the regulation of the G 2 phase pool of cyclin A/cdk2 is critical for cyclin B/cdk1 activation and G 2 /M progression.…”

Section: Discussionsupporting

confidence: 93%

“…A number of laboratories have provided evidence that G 2 phase cyclin A/cdk2 has a critical role in the timing of entry into mitosis (Furuno et al, 1999;Goldstone et al, 2001;Hu et al, 2001;Mitra and Enders, 2004;Fung et al, 2007;Gong et al, 2007), which is confirmed by our siRNA and cdk2-specific inhibitor studies. In agreement with these reports, the present study demonstrates that inhibition of G 2 phase cyclin A/cdk2 delays the cdc25-dependent activation (Mitra and Enders, 2004;Fung et al, 2007), and nuclear translocation (Gong et al, 2007) of cyclin B/cdk1.…”

Section: Discussionsupporting

confidence: 83%

“…Cyclin A/cdk2 appears to be involved in the activation (Furuno et al, 1999;Mitra and Enders, 2004), and possibly the stabilization of cyclin B, the latter by indirectly inhibiting the anaphase-promoting complex/cyclosome (APC/C) (Lukas et al, 1999). Cyclin A is itself destroyed by the APC/C at prometaphase (den Elzen and Pines, 2001) inferring that its activity is required until that time.…”

Section: Introductionmentioning

confidence: 99%

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Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

et al. 2008

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Cyclin A/cdk2 has a role in progression through S phase, and a large pool is also activated in G 2 phase. Here we report that this G 2 phase pool regulates the timing of progression into mitosis. Knock down of cyclin A by siRNA or addition of a specific cdk2 small molecule inhibitor delayed entry into mitosis by delaying cells in G 2 phase. The G 2 phase-delayed cells contained elevated levels of inactive cyclin B/cdk1. However, increased microtubule nucleation at the centrosomes was observed, and the centrosomes stained for markers of cyclin B/cdk1 activity. Both microtubule nucleation at the centrosomes and the phosphoprotein markers were lost with short-term treatment of the cdk1/2 inhibitor roscovitine but not the Mek1/2 inhibitor U0126. Cyclin A/cdk2 localized at the centrosomes in late G 2 phase after separation of the centrosomes but before the start of prophase. Thus G 2 phase cyclin A/cdk2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/cdk1, but also has an unexpected role in coordinating the activation of cyclin B/cdk1 at the centrosome and in the nucleus.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

et al. 2008

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“…Notably, while neither cyclin E1 nor E2 is essential for cell cycle progression during mouse development Parisi et al 2003; see below), cyclin A2 disruption results in early embryonic lethality (Murphy et al 1997). In S phase, cyclin A-Cdk2 is thought to phosphorylate substrates that start DNA replication from preassembled replication initiation complexes (Krude et al 1997;Hua and Newport 1998;Coverley et al 2002) and to be required for coordinating the end of S phase with activation of the mitotic Cdks (Mitra and Enders 2004). Because it appears to orchestrate the numerous activities required for S-phase entry, S-phase progression, and entry into mitosis, Cdk2, in particular, has been viewed as a master regulator whose activities were thought to be essential.…”

Section: G1 Regulation In Mammalian Cellsmentioning

confidence: 99%

Living with or without cyclins and cyclin-dependent kinases

Sherr¹,

Roberts²

2004

Genes Dev.

993

882

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Entry into, progression through, and exit from the G1 phase of the mammalian cell cycle in response to extracellular mitogenic cues are presumed to be governed by cyclin-dependent kinases (Cdks) regulated by the D-type and E-type cyclins. Studies performed over more than a decade have supported the view that these holoenzymes are important, if not required, for these processes. However, recent experiments in which the genes encoding all three D-type cyclins, the two E-type cyclins, cyclin Ddependent Cdk4 and Cdk6, or cyclin E-dependent Cdk2 have been disrupted in the mouse germ line have revealed that much of fetal development occurs normally in their absence. Thus, none of these genes is strictly essential for cell cycle progression. To what extent is the prevailing dogma incorrect, and how can the recent findings be reconciled with past work?

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“…The human phosphatase Cdc25A is an oncogenic protein (Galaktionov et al, 1995). Both Cdc25a and b genes are involved in tumor growth and play critical roles in regulating apoptosis and cell cycle progression (Mitra and Enders, 2004;Brezak et al, 2005). Increased expression of Cdc25A, B and C in active dephosphorylated forms are observed in aggressive human cancers (Kallstrom et al, 2005).…”

Section: Tff1 Transforming Functions and Cdc25 Phosphatases S Rodrigumentioning

confidence: 99%