Anti-Chk2: Monoclonal Checkpoint Kinase 2 Antibody |
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BACKGROUND Checkpoint kinase 2 (Chk2) is a Serine/Threonine kinase that along with Chk1 participated in DNA damage signaling, regulation of cell cycle and DNA damage induced apoptosis. Upon phosphorylation and activation by the upstream sensor-associated kinases ATM (Ataxia Telangiectasia Mutated) and ATR (ATM and Rad3-related), Chk2 will amplify the DNA damage signal by phosphorylating several substrates that mediate cell-cycle arrest, DNA repair and apoptosis.1 Chk2 kinases were first identified as checkpoint kinases in Schizosaccharomyces pombe and Saccharomyces cerevisiae. The S. pombe Chk2 (Cds1) protein, along with Chk1, regulates the G2/M transition via phosphorylation of Cdc25 in response to replication interference and DNA damage, respectively.2 Chk2 (Cds1) phosphorylates the mitosis-promoting phosphatase Cdc25c in an inhibitory residue, providing a binding site for 14-3-3 protein. The nuclear exclusion mediated by 14-3-3 blocks Cdc25c interaction with its substrate, thus preventing cells from entering mitosis in the presence of damaged DNA. Chk2 phosphorylates Cdc25A, promoting a proteasome-dependent degradation of the phosphatase with consequent arrest of the cell cycle in the G1 and S phases. The fission and budding yeast Chk2 orthologs (Cds1 and Rad53) also have a role in the recovery from replication blocks and stalled replication forks. Chk2 has been postulated to have a role in the repair of DNA strand breaks via phosphorylation of Brca1.3 Cells lacking CHK2 have a defect in apoptosis, suggesting that Chk2 has a role in DNA damage-induced apoptosis, presumably by up-regulating p53 levels or by phosphorylating the E2F1 transcription factor or promyelocytic leukemia (PML) protein.4
REFERENCES
1. Perona R et al.: Clin Transl Oncol. 10:538-42, 2008.
2. Kumar S & Huberman JA: J Biol Chem. 279:43574-80, 2004.
3. Miyabe I et al.: J Cell Sci. 122:3638-43, 2009.
4. Roos WP & Kaina B: Trends Mol Med. 12:440-50, 2006.
2. Kumar S & Huberman JA: J Biol Chem. 279:43574-80, 2004.
3. Miyabe I et al.: J Cell Sci. 122:3638-43, 2009.
4. Roos WP & Kaina B: Trends Mol Med. 12:440-50, 2006.
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
Параметры
Cat.No.: | CC10005 |
Antigen: | An E. coli-expressed recombinant protein containing human CHK2 (aa481-531) sequence. |
Isotype: | Mouse monoclonal IgG2b |
Species & predicted species cross- reactivity ( ): | Human, Mouse, Monkey |
Applications & Suggested starting dilutions: | WB 1:1000 IP n/d IHC (Paraffin) 1:200 - 1:1000 ICC 1:200 FACS n/d |
Predicted Molecular Weight of protein: | 62 kDa |
Specificity/Sensitivity: | This monoclonal antibody detects endogenous levels of Chk2 proteins in various cell lysates. |
Storage: | Store at -20°C, 4°C for frequent use. Avoid repeated freeze-thaw cycles. |
*Optimal working dilutions must be determined by end user.
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