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What is an Inhibitor of Apoptosis?

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  • Written By: Daniel Liden
  • Edited By: Jenn Walker
  • Last Modified Date: 04 December 2016
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An inhibitor of apoptosis protein, or IAP, is a type of protein that is able to stop apoptosis, or programmed cell death. Programmed cell death is an important process in development, immune defense, and cancer protection, but it must be regulated to prevent uncontrolled cell death. Generally, an inhibitor of apoptosis will work by inhibiting caspases, proteins that are necessary for the initiation of apoptosis. They also regulate some transcription factors that are important for the synthesis of various proteins that lead to apoptosis. It is believed that inhibitors of apoptosis may be related to tumor formation because one of the characteristics of many cancerous cells is the inability to undergo apoptosis.

Caspases are the primary proteins involved in the initiation of apoptosis, so naturally, they are the primary targets of almost every inhibitor of apoptosis. Different caspases work in different ways; initiator caspases are necessary to activate effector caspases, which act on various substrates to actually inhibit apoptosis. An inhibitor of apoptosis may interfere at any stage of this process, thereby halting the process of programmed cell death. Though there are many types of IAPs, their structures are highly similar and they function through very similar mechanisms.

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There are also regulatory proteins that exist for the purpose of regulating inhibitors of apoptosis. The second mitochondria-derived activator of caspase, or SMAC, for example, binds to an inhibitor of apoptosis protein in order to increase caspase activity, thereby promoting apoptosis. The complex and overlapping mechanisms of apoptosis regulation are necessary because unregulated or completely inhibited apoptosis can both be highly detrimental to an organism's health. It is important to ensure that beneficial, healthy cells are not unnecessarily destroyed and that detrimental or unnecessary cells are removed before their full effects can be felt. For this reason, it is also important that the regulatory factors themselves are subject to regulation, as they are the primary determinants of apoptosis.

It is possible that an inhibitor of apoptosis may have a role in cancer because cancerous cells do not undergo apoptosis as damaged or mutated cells otherwise should. A great deal of the evidence for this theory comes from an inhibitor of apoptosis protein called survivin, which is highly prevalent in almost all human tumors. Inhibition of this inhibitor of apoptosis has been shown to lead to a reduction of the sizes of some tumors, as its absence opens up the pathway to apoptosis so the cancerous cells can undergo programmed cell death.

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