Cyclin, regulatory subunit

The cell cycle and cell proliferation are controlled by the activity of cyclin-depen-dent kinases (cdks) (for a review, see Ref [54]). The cdks are activated by association with cyclin regulatory subunits and phosphorylation, and inhibited by binding of inhibitors such as and p27 ". ... 

Cyclin-dependent kinases (CDKs) play a key role in regulating cell cycle machinery. This family of kinases requires association with a cyclin regulatory subunit for activity. Different CDK/cyclin pairs are active during each phase of the cell cycle. Negishi cross-coupling reactions were the key steps in the synthesis of [l,3,5]triazine-pyridine biheteroaryls 161 as a novel series of potent cyclin-dependent kinase inhibitors. ... 

Cyclin B is the positive regulatory subunit of protein kinase Cdkl. It was the first cychn discovered, as a protein that is destroyed at the end of each cell cycle in early embryos of marine invertebrates, such as sea urchins... 

The cyclins are regulatory subunits of protein kinases of the cell cycle (see Chapter 14). 

Figure 24.23. Cyclin expression is regulated according to the cell cycle. (A) The regulatory subunits of the cyclin-dependent kinases (CDKs) are referred to as cyclins because these proteins are synthesized and degraded during the cell cycle. (Adapted from Weinberg RA Biology of Cancer 2007.) (B) Specific cyclins bind to and activate specific CDKs, and this propels the cell through specific stages of the cell cycle.

Cyclin-Cdks were appropriately named the cell cycle s engines . The cyclin-dependent protein kinases (Cdks) are soluble serine/threonine kinases of 34-40 kDa. The Cdks share with other serine/threonine protein kinases sequence similarities, including a subset of residues that is essential for catalytic activity. Cdks contribute the catalytic subunit, whereas the regulatory subunit is contributed by a cyclin. Cyclins control the kinase activity, determine the substrate specificity and the subcellular location of Cdks. Each of these processes is a potential site of regulation. The major substrates of the Cdks are proteins regulating gene transcription. Cdks can be controlled in three major ways ... 

The concentrations of the cyclins, the regulatory subunits of the heterodlmerlc protein kinases that control cell-cycle... 

Progression through the cell cycle is regulated by the cyclin-dependent protein kinases (CDKs), which act at specific points in the cycle, phosphorylating key proteins and modulating their activities. The catalytic subunit of CDKs is inactive unless associated with the regulatory cyclin subunit. 

A FIGURE 21-2 Overview of current model for regulation of the eukaryotic cell cycle. Passage through the cycle is controlled by G-i, S-phase, and mitotic cyclin-dependent kinase complexes (green). These are composed of a regulatory cyclin subunit and a catalytic cyclin-dependent kinase (CDK) subunit. 

Because the oocyte injection assay initially used to measure MPF activity is cumbersome, several years passed before MPF was purified by column chromatography and characterized. MPF is in fact one of the heterodlmerlc complexes composed of a cyclin and CDK now known to regulate the cell cycle. Each MPF subunit initially was recognized through different experimental approaches. First we discuss how the regulatory cyclin subunit was identified and then describe how yeast genetic experiments led to discovery of the catalytic CDK subunit. 

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