posted 08-11-2009 06:29 PM            

AnaSpec is pleased to announce the release of a series of zebrafish specific Z-Fish™ antibodies for use in cell cycle control research. The protein targets for these antibodies include cyclin D, Rb1 (retinoblastoma associated protein) and p27-some of the key players in cell cycle regulation.

Cell proliferation is tightly controlled by cyclin dependent kinases (CDKs) that function sequentially during cell cycle. These kinases phosphorylate and thereby regulate key substrates involved in cell cycle progression1. The regulation of CDKs involves interaction with additional proteins and post-translational modifications. Essential positive regulators of CDKs are the cyclins, regulatory subunits of cyclin/CDK kinase complexes that are expressed periodically during the cell cycle. Furthermore, CDKs are controlled by phosphorylation that either stimulates or represses catalytic activity2. CDK inhibitors (CKIs) have been shown to interact with distinct cyclin/CDK complexes, thereby interfering with their catalytic activity3. Induction of the proto-oncogene cyclin D1, and its binding to CDK4 or CDK6, is a rate-limiting event during cell-cycle progression through G1 phase. Some studies suggested that cyclin D1 also has CDK-independent functions4. Studies in zebrafish model show that cyclin D1 is upregulated by meis1. Cyclin D1 also controls several development processes and in some way, carcinogenesis5. p27KIP1 (p27) is a CKI that was originally identified as a protein capable of inhibiting G1 cyclin/CDK complexes. p27 was discovered as a protein whose expression is induced by different growth inhibitory agents, including tumor growth factor beta6–9. Thus, p27 links proliferative and anti-proliferative signals and controls the transition from the G1 into the S phase of the cell cycle.

AnaSpec provides 2 anti-cyclin D1 antibodies, one raised with a peptide sequence from the N-terminus (NT) and the other from the C-terminus (CT). Anti-p27 Kip1 is raised from a C-terminal peptide sequence.

The retinoblastoma-associated protein (Rb1) is one of the key cell-cycle regulating proteins that act as a tumor suppressor. Its inactivation leads to neoplastic transformation and carcinogenesis. This protein regulates critical G1-to-S phase transition through interaction with the E2F family of cell-cycle transcription factors repressing transcription of genes required for this cell-cycle checkpoint transition10,11. Its activity is regulated through network sensing intracellular and extracellular signals that block or permit phosphorylation (inactivation) of the Rb protein. It also regulates apoptosis through the same interaction with E2F transcription factors and Rb–E2F complexes play a role in regulating the transcription of genes involved in differentiation and development12,13.

References
1. Nurse, P. Cell 100, 71 (2000).
2. Obaya, AJ. and JM. Sedivy, Cell. Mol. Life Sci. 59, 126 (2002).
3. Sherr, CJ. and JM. Roberts, Genes Dev. 13, 1501 (1999).
4. Fu, M., et al. Endocrinology 145, 5439 (2004).
5. Bessa, J. et al. Development 135, 799 (2008).
6. Polyak, K. et al. Genes Dev. 8, 9 (1994).
7. Polyak, K. et al. Cell 78, 59 (1994).
8. Slingerland, JM. et al. Mol. Cell. Biol. 14, 3683 (1994).
9. Toyoshima, H. and T. Hunter, Cell 78, 67 (1994).
10. Giacinti C and A. Giordano Oncogene 25 5220 (2006).
11. Weinberg, RA. Cell 81 323 (1995).
12. Clarke, AR, et al. Nature (London) 359 328 (1992).
13. Chau, BN and JY. Wang Nat. Rev. Cancer 3 130 (2003).

About AnaSpec

AnaSpec is a leading provider of integrated proteomics solutions to the world’s largest biotech, pharmaceutical, and academic research institutions. With a vision for innovation through synergy, AnaSpec focuses on three core technologies: peptides, detection reagents, and antibodies.

For more information visit www.anaspec.com

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