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Cell Cycle Regulation Antibody Sampler Kit  货号: HAK21

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  • 背景

  • Eukaryotic cell cycle progression is dependent, in part, on the tightly regulated activity of cyclin dependent kinases (CDKs). Cyclin D/CDK4/6 activity occurs in mid-late G1 phase, upstream of CDK2/cyclin E activity. Both of these activities are required for hyperphosphorylation of the retinoblastoma gene product (pRb). pRb phosphorylation allows the release of S phase-promoting transcription factors and is indicative of the cell's commitment to proliferate. This point in the cell cycle is known as the restriction point. Cyclin protein levels oscillate throughout the cell cycle, and their availability is a means of controlling CDK activity and cell proliferation. Cyclin D is degraded through the ubiquitin proteasome pathway in the absence of mitogenic signaling. Ubiquitination of cyclin D1 is enhanced by phosphorylation at Thr286 by glycogen synthase kinase 3b (GSK-3b). p27/Kip1, p57 Kip2 and p21 Waf1/Cip1 are members of the Cip/Kip family of cyclin-dependent kinase inhibitors. They form heterotrimeric complexes with cyclins and CDKs, inhibiting kinase activity and blocking progression through G1/S phase. However, p21 may enhance assembly and activity of cyclin D/CDK4/6 complexes. Levels of p21 and p27 protein are controlled through ubiquitination and proteasomal degradation. Levels of p27 are upregulated in quiescent cells and in cells treated with negative cell cycle regulators. p27 nuclear localization is controlled by Akt-dependent phosphorylation at Thr157. The inhibitors of CDK4 (INK4) family include p15 INK4B, p16 INK4A, p18 INK4C, and p19 INK4D. All INK4 proteins selectively inhibit CDK4/6 activity, either in a binary complex, or in a ternary complex including cyclin D, resulting in inhibition of cell division.
  • 背景文献

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    2. Pestell, R.G. et al. (1999) Endocr Rev 20, 501-34.

    3. Cheng, M. et al. (1999) EMBO J 18, 1571-83.

    4. Sheaff, R.J. et al. (2000) Mol Cell 5, 403-10.

    5. Shin, I. et al. (2002) Nat Med 8, 1145-52.

    6. Guan, K.L. et al. (1994) Genes Dev 8, 2939-52.

    7. Hirai, H. et al. (1995) Mol Cell Biol 15, 2672-81.