000			02056nam a2200253Ia 4500
003			MX-MdCICY
005			20250625122509.0
040			_cCICY
090			_aB-6020
245	1	0	_aCyclin A/Cdk2 complexes regulate activation of Cdk1 and Cdc25 phosphatases in human cells
490	0		_vOncogene, 23(19), p.3361-3367, 2004
520	3		_aMitotic entry, a critical decision point for maintaining genetic stability, is governed by the cyclin B/Cyclin dependent kinase 1 (Cdc2)complex. In Xenopus oocytes and early embryos, accumulation of cyclin B activates Cdk1, which then phosphorylates and activates the positive regulator Cdc25 in an autocatalytic feedback loop. However, cyclin B levels do not increase as some human cells approach mitosis, and the key factors regulating Cdk1 activation in human cells are unknown. We report here that reducing cyclin A expression by RNA interference (RNAi)in primary human fibroblasts inhibited activation of Cdc25B and Cdc25C and dephosphorylation of Cdk1 on tyrosine (tyr)15. These results were reproduced in U2-OS cells by inducing the expression of a dominant-negative (dn)mutant of Cdk2, the principal cyclin A binding partner. Cdk2-dn induction could inhibit Cdc25B activity and foster Cdk1 tyr phosphorylation within the S phase, temporally dissociating these events from Cdk1 activation at mitosis. In contrast, reducing Cdk1 expression delayed mitotic entry without markedly impairing Cdc25B or Cdc25C activity. These results suggest that cyclin A/Cdk2 complexes are key regulators of Cdc25 and Cdk1 activation in human cells. This pathway appears to be commonly deregulated in cancer.
650	1	4	_aCELL CYCLE
650	1	4	_aCDK1
650	1	4	_aCDK2
650	1	4	_aCDC25B
650	1	4	_aCDC25C
650	1	4	_aG2
700	1	2	_aMitra, J.
700	1	2	_aEnders, G.H.
856	4	0	_uhttps://drive.google.com/file/d/1aRd1CLL_7sQEfP_-UXirdhk6oMBJx4el/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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999			_c40365 _d40365