noted to control the lengths of telomeres formed by these telomerases. Shelterin works to protect telomeres against unsuitable activation of the DNA damage response pathway, as noted in the function section above. TERF2 as part of the shelterin complex, has been known to block the ATM signaling pathways and prevent chromosome end fusion. In cancer cells, TERF2 phosphorylation by extracellular signal-regulated kinase (ERK1/2) is a controlling factor in the major pro-oncogenic signaling pathways (RAS/RAF/MEK/ERK) that affect telomeric stability. Additionally, when TERF2 was non-phosphorylated in melanoma cells, there was a cell induced DNA damage response, arresting growth and causing tumor reversion. Studies have found that in tumor cells, TERF2 levels are observed to be high, and this raised level of TERF2 contributes to oncogenesis in a variety of ways. This high level of TERF2 decreases the ability to recruit and activate natural killer cells in human tumor cells. One study used a dominant negative form of TERF2ΔBΔC, to inhibit TERF2, and found that it could induce a reversion malignant phenotype in human melanoma cells. Therefore, over-expression of TERF2ΔBΔC, causing blocking of TERF2, induced apoptosis and reduced tumourigenicity in certain cell lines. Additionally, upregulation of TERF2 may be the cause of the establishment and maintenance of short telomeres. These short telomeres increase chromosomal instability, and increase the chances of certain cancers progressing in the body, such as with leukemia. In gastric mucosa tissues, the expression of TERF2 proteins was significantly higher than normal, and this over-expression of TERF2, along with over-expression of TERF1, TIN2, TERT, and BRCA1 protein transposition, may cause a reduction in telomere length, further contributing to multistage carcinogenesis of gastric cancer. References Further reading External links PDBe-KB provides an overview of all the structure information available in the PDB for Human Telomeric repeat-binding factor 2 (TERF2) Telomere-binding proteins