Anaspec has released 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, which are described as some of the key players in cell-cycle regulation.
Cell proliferation is tightly controlled by cyclin-dependent kinases (CDKs) that function sequentially during the cell cycle.
These kinases phosphorylate and regulate key substrates involved in cell-cycle progression.
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.
CDKs are controlled by phosphorylation, which either stimulates or represses catalytic activity.
CDK inhibitors (CKIs) have been shown to interact with distinct cyclin/CDK complexes, thereby interfering with their catalytic activity.
Induction of the proto-oncogene cyclin D1 - and its binding to CDK4 or CDK6 - is a rate-limiting event during cell-cycle progression through the G1 phase.
Some studies have suggested that cyclin D1 also has CDK-independent functions.
Studies in zebrafish models show that cyclin D1 is upregulated by meis.
Cyclin D1 also controls several development processes and, in some way, carcinogenesis.
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 tumour growth factor beta 6-9.
Therefore, p27 links proliferative and anti-proliferative signals and controls the transition from the G1 into the S phase of the cell cycle.
Anaspec provides two 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 Rb1 is one of the key cell-cycle regulating proteins that acts as a tumour 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 the transcription of genes required for this cell-cycle checkpoint transition.
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 development.
