The article by Sherr and Roberts discusses the role of mammalian G1 cyclin-dependent kinases (CDKs) and their negative regulators, CDK inhibitors, in the regulation of the cell cycle. The discovery of G1 cyclins and associated CDKs has provided insights into how the cell cycle progresses through the first gap phase (G1). The authors highlight the importance of D-type cyclins and cyclin E in G1 progression, which are regulated by mitogenic signals. They also describe the functions of p21 (Cip1, Waf1, Sdi1, Cap20), p27 (Kip1), and p57 (Kip2) as CDK inhibitors, which play crucial roles in controlling cell cycle arrest and preventing uncontrolled cell division. The article explains how these inhibitors bind to and inhibit CDKs, and how their levels can be regulated to control the cell cycle. Additionally, it discusses the role of p16INK4a and other members of the INK4 family in regulating CDK4 and CDK6 activity, and how their loss or dysfunction can contribute to tumor development. The authors suggest that the presence of multiple CDK inhibitors may allow for differential responses to antiproliferative signals and the coordination of cell cycle progression with DNA replication and repair processes.The article by Sherr and Roberts discusses the role of mammalian G1 cyclin-dependent kinases (CDKs) and their negative regulators, CDK inhibitors, in the regulation of the cell cycle. The discovery of G1 cyclins and associated CDKs has provided insights into how the cell cycle progresses through the first gap phase (G1). The authors highlight the importance of D-type cyclins and cyclin E in G1 progression, which are regulated by mitogenic signals. They also describe the functions of p21 (Cip1, Waf1, Sdi1, Cap20), p27 (Kip1), and p57 (Kip2) as CDK inhibitors, which play crucial roles in controlling cell cycle arrest and preventing uncontrolled cell division. The article explains how these inhibitors bind to and inhibit CDKs, and how their levels can be regulated to control the cell cycle. Additionally, it discusses the role of p16INK4a and other members of the INK4 family in regulating CDK4 and CDK6 activity, and how their loss or dysfunction can contribute to tumor development. The authors suggest that the presence of multiple CDK inhibitors may allow for differential responses to antiproliferative signals and the coordination of cell cycle progression with DNA replication and repair processes.