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(Circulation Research. 2003;92:345.)
© 2003 American Heart Association, Inc.

Editorials

The Cyclin-Dependent Kinase Pathway Moves Forward

Karin E. Bornfeldt

From the Department of Pathology, University of Washington School of Medicine, Seattle, Wash.

Correspondence to Karin E. Bornfeldt, Department of Pathology, Box 357470, University of Washington School of Medicine, Seattle, WA 98195-7470. E-mail bornf@u.washington.edu

Key Words: migration • cyclin-dependent kinase inhibitor • retinoblastoma protein • smooth muscle cells

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The cell cycle of mammalian cells is divided into four phases: G₁ (first gap), S (DNA synthesis), G₂ (second gap), and M (mitosis). Quiescent cells that have not entered the cell cycle are referred to as being in G₀. Progression through the cell cycle requires the activation of cyclin-dependent kinases (CDKs). CDK activation is dependent on the association of the CDK with a cyclin regulatory subunit. Cyclin D/CDK4, cyclin D/CDK6, and cyclin E/CDK2 regulate transition through G₁, cyclin A/CDK2 regulates S phase transition, and cyclin A/CDK2 and cyclin B/CDK2 regulate G₂/M transition,¹ as shown by the Figure. The activity of CDKs is also regulated by endogenous CDK inhibitors (CKIs) in the cyclin/CDK complex¹ (Figure). Two families of CKIs have been characterized according to their structures and CDK targets. Kip/Cip proteins (p21^Cip1, p27^Kip1, and p57^Kip2), which bind to both cyclin and CDK subunits, inhibit cyclin E- and A-dependent kinases but act as positive regulators of cyclin D-dependent kinases. The INK family of proteins (p16^INKa, p15^INKb, p18^INKc, and p19^INKd) exclusively binds to and inhibits CDK4 and CDK6.¹

View larger version (32K): [in this window] [in a new window]   How does the cell cycle control cell migration? Cells in mid-late G1 have the greatest ability to migrate, whereas cells in the G0, S, G2, and M phases are stationary. Overexpression of CKIs (p21Cip1 and p27Kip1) blocks CDK2 activity, G1 to S transition, and migration of SMCs. Furthermore, as shown by the studies of Díez-Juan and Andrés,16 overexpression of . . . [Full Text of this Article]

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