Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

     breast cancer Genetics Home Reference provides information about breast cancer . Li-Fraumeni syndrome Although most cases of Li-Fraumeni syndrome are associated with mutations in the TP53 gene, CHEK2 gene mutations have been identified in several families with cancers characteristic of this condition. At least one family has a mutation that deletes a single DNA building block (nucleotide) at position 1100 in the CHEK2 gene (written as 1100delC). The 1100delC mutation leads to the production of an abnormally short, nonfunctional version of the CHK2 protein. Researchers are uncertain whether CHEK2 gene mutations actually cause Li-Fraumeni syndrome or are merely associated with an increased risk of several types of cancer, including those cancers often seen in Li-Fraumeni syndrome. ovarian cancer Genetics Home Reference provides information about ovarian cancer. prostate cancer Genetics Home Reference provides information about prostate cancer. other cancers Mutations in the CHEK2 gene, including the 1100delC mutation described above, have also been found in other hereditary and nonhereditary (sporadic) cancers affecting many of the body's organs and tissues. Although the full range of cancers associated with CHEK2 mutations has not been determined, studies have associated mutations in this gene with prostate, breast, lung, colon, kidney, thyroid, and ovarian cancers. CHEK2 mutations have also been found in some brain tumors and in a type of bone cancer called osteosarcoma.

     The CHEK2 gene provides instructions for making a protein called checkpoint kinase 2 (CHK2). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way. The CHK2 protein is activated when DNA becomes damaged or when DNA strands break. DNA can be damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, and breaks in DNA strands also occur naturally when chromosomes exchange genetic material. In response to DNA damage, the CHK2 protein interacts with several other proteins, including tumor protein 53 (which is produced from the TP53 gene). These proteins halt cell division and determine whether a cell will repair the damage or self-destruct in a controlled manner (undergo apoptosis). This process keeps cells with mutated or damaged DNA from dividing, which helps prevent the development of tumors.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• CBF-B
• NF-YB
• STAT1
• STAT1beta
• STAT1alpha
• E2F-1
• CBF-C

Tissue specificity:

High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.

Enzyme Regulation:

Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68.

Molecular Function:

• Atp Binding
• Identical Protein Binding
• Metal Ion Binding
• Protein Homodimerization Activity
• Protein Kinase Binding
• Protein Serine/Threonine Kinase Activity
• Ubiquitin Protein Ligase Binding

Biological Processes:

• Cell Division
• Cellular Protein Catabolic Process
• Cellular Response To Bisphenol A
• Cellular Response To Dna Damage Stimulus
• Cellular Response To Gamma Radiation
• Dna Damage Checkpoint
• Dna Damage Induced Protein Phosphorylation
• Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Cell Cycle Arrest
• Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Transcription Of P21 Class Mediator
• Double-Strand Break Repair
• G2/M Transition Of Mitotic Cell Cycle
• Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage
• Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage By P53 Class Mediator
• Mitotic Spindle Assembly
• Negative Regulation Of Cell Cycle Arrest
• Negative Regulation Of Dna Damage Checkpoint
• Peptidyl-Serine Phosphorylation
• Positive Regulation Of Anoikis
• Positive Regulation Of Protein Phosphorylation
• Positive Regulation Of Transcription, Dna-Templated
• Protein Autophosphorylation
• Protein Phosphorylation
• Protein Stabilization
• Regulation Of Protein Catabolic Process
• Regulation Of Signal Transduction By P53 Class Mediator
• Regulation Of Transcription, Dna-Templated
• Replicative Cell Aging
• Replicative Senescence
• Signal Transduction In Response To Dna Damage
• Signal Transduction Involved In Intra-S Dna Damage Checkpoint
• Transcription, Dna-Templated
• Response To Gamma Radiation

*synonyms