Cell Signaling Technology

Product Pathways - DNA Damage

Claspin Antibody #2800

Applications Reactivity MW (kDa) Source
W H 220 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human
Species enclosed in parentheses are predicted to react based on 100% sequence homology. Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

Claspin Antibody detects endogenous levels of total claspin protein.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic peptide (KLH-coupled) corresponding to amino acids near the carboxy terminus of human claspin. Antibodies are purified by peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts of HEL, SH-SY5Y and NCCIT cells using Claspin Antibody.

Background

Originally identified in Xenopus (1), and later in human cells (2), claspin is a mediator of Chk1 signal transduction at the replication checkpoint and in response to DNA damage. Expression of claspin is cell cycle-regulated, with protein levels peaking at the S/G2 phase (2). Expression is negatively regulated by both proteosome- and caspase-mediated degradation (3), and stabilized by activation of Chk1 (4). Claspin is a chromatin-bound protein, and has been shown to interact with the PNCA complex in the absence of DNA damage (5). Following checkpoint activation it remains chromatin-bound but is released from the PCNA complex and is phosphorylated in an ATR-dependent manner. Phosphorylated claspin interacts with several components of the DNA damage response including BRCA1 (6) and Chk1 (7), leading to ATR-dependent phosphorylation on each of these proteins. Phosphorylated Rad17 has also been shown to bind to and regulate the phosphorylation of claspin (8). It has been proposed that claspin behaves as a tumor suppressor in come cases since down-regulation promotes apoptosis following genotoxic stress (2). Conversely, claspin seems to behave as an oncogene in other instances since overexpression promotes cellular proliferation (6). Upregulated claspin has been suggested to be a sensitive marker of abnormally proliferating cells (9).

  1. Kumagai, A. and Dunphy, W.G. (2000) Mol Cell 6, 839-49.
  2. Chini, C.C. and Chen, J. (2003) J Biol Chem 278, 30057-62.
  3. Semple, J.I. et al. (2007) Cell Death Differ, Epub ahead of print.
  4. Chini, C.C. et al. (2006) Oncogene 25, 4165-71.
  5. Brondello, J.M. et al. (2007) Biochem Biophys Res Commun 354, 1028-33.
  6. Lin, S.Y. et al. (2004) Proc Natl Acad Sci U S A 101, 6484-9.
  7. Jeong, S.Y. et al. (2003) J Biol Chem 278, 46782-8.
  8. Wang, X. et al. (2006) Mol Cell 23, 331-41.
  9. Tsimaratou, K. et al. (2007) J Pathol 211, 331-9.

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