not shut down from a single off signal. GAP activity is highly dynamic, interacting with many other components of signaling pathways. Disease associations and clinical relevance The importance of GAPs comes from its regulation of the crucial G proteins. Many of these G proteins are involved in cell cycling, and as such are known proto-oncogenes. The Ras superfamily of G proteins, for example, has been associated with many cancers because Ras is a common downstream target of many growth factors like FGF, or fibroblast growth factor. Under normal conditions, this signaling ultimately induces regulated cell growth and proliferation. However, in the cancer state, such growth is no longer regulated and results in the formation of tumors. Often, this oncogenic behavior is due to a loss of function of GAPs associated with those G proteins or a loss of the G protein's ability to respond to its GAP. With the former, G proteins are unable to hydrolyze GTP quickly, resulting in sustained expression of the active form of G proteins. Although the G proteins have weak hydrolytic activity, in the presence of functional GEFs, the inactivated G proteins are constantly replaced with activated ones because the GEFs exchange GDP for GTP in these proteins. With no GAPs to curb the G protein's activity, this results in constitutively active G proteins, unregulated cell growth, and the cancerous state. In the case of the latter, a loss of the G protein's ability to respond to GAP, the G proteins have lost their ability to hydrolyze GTP. With a nonfunctional G protein enzyme, GAPs cannot activate the GTPase activity, and the G protein is constitutively on. This also results in unregulated cell growth and cancer. Examples of GAP malfunction are ubiquitous clinically. Some cases involve a decreased expression of the GAP gene. For example, some recently characterized cases of papillary thyroid cancer cells in patients show a decreased expression of Rap1GAP, and this expression is seemingly caused by a decreased expression of the GAP mRNA, shown by qRT-PCR experiments. In this case, there appears to be a loss of proper Rap1GAP gene expression. In another case, expression of the Ras GAP is lost in several cancers due to improper epigenetic silencing of the gene. These cells have CpG methylations near the gene that, in effect, silence gene transcription. Regulation of G proteins is lost because the regulator is absent, resulting in cancer. Other cancers