4 Apoptosis Protein Families

If you are really familiar with apoptotic pathway, I’m sure you will know how essential role are the apoptosis protein play in this programmed cell death. Today, I’m going to show you 4 apoptosis protein families in details which are pro-apoptosis protein, anti-apoptosis protein, caspases and p53 tumour suppressor protein.

Pro-apoptosis Protein

The pro-apoptosis protein is a protein family that promotes the apoptosis to occur. The pro-apoptosis Bax protein is one of the major players in apoptosis (Mojgan et. al., 2002). Studies have proved that when Bax is activated, it creates discontinuity or pores in the outer mitochondrial membrane to regulate the release of cytochrome c. The intrinsic apoptotic pathway will not be activated in the absence of Bax-activating signals. In addition, cells lack of Bax protein will not undergo apoptosis even though there are death stimuli (Lei et. al., 2006).

Caspases

Caspases are a family of cysteine proteases that play a crucial role in apoptosis. When the caspases are exposed to a pro-apoptotic signal, the zymogen forms of caspases will proteolytically cleave and activated. The initiator caspases like caspase 8, caspase 9, and caspase 10 can split other caspases. The executioner caspases such as caspase 3, caspase 6 and caspase 7 cleave the death substrates. All caspases consists of a single cysteine at the enzyme catalytic site (Byung et. al., 2002). Both intrinsic and extrinsic pathways trigger pro-apoptotic caspases or pro-caspases via a process called caspase cascade (Avi et. al., 2008).

P53 Tumour Suppressor Proteins

The p53 protein is a transcription factor and pro-apoptosis protein. It proliferates the transcriptional expression of several genes that involved when react to genotoxic agents like ionizing radiation and chemical therapeutic drugs. The p53 protein initiates the cell cycle arrest and DNA damage repair. If the cells cannot be repaired, the p53 protein will activates cell death programs and the cells then go through the apoptosis. Hence, p53 protein is a tumor suppressor protein against cancer development. The effective ways to prevent tumor growth and discard cancers are inhibit the cell proliferation and promote the apoptosis in tumors. Conventionally, chemotherapeutic agents that used to induce apoptosis are mediated mostly via p53-dependent pathways. Yet, most of human tumors have p53 mutations and inactivation (Luo et. al., 2008). The p53 protein activates the expression of pro-apoptosis protein, such as Bax and down regulates the expression of the anti-apoptosis protein like Bcl-2 (Byung et. al., 2002).

Anti-apoptosis Protein

Anti-apoptosis protein is a protein family that discourages the apoptosis to occur. Bcl-2 protein can protect the cell against apoptosis. Many experiments have proven that Bcl-2 protein controls intracellular Ca²⁺ levels and disallows the ruined of mitochondrial membrane when induced by pro-apoptotic proteins. Some evidences have shown that Bcl-2 protein is an ion channel which controls the release of cytochrome c from mitochondrial. This ion channel may modulate the apoptosis by regulating the permeability of intracellular membranes and cytochrome c release from mitochondria. Therefore, many Bcl-2 anti-apoptotic mechanisms have been suggested. Yet, the overexpression of Bcl-2 protein can save the cells from death (Jong et. al., 2001). The high expression of Bcl-2 proteins in tumours is related to resistance to cancer therapy. This is a major obstacle for the cancer treatment when the cancer is surgically incurable (Huang et. al., 2005).

In conclusion, these families of apoptosis protein are crucial in apoptotic pathway. The regulation of these apoptosis protein families may help in cancer treatment. Further cancer research need to be carried out so that we can regulate these apoptosis protein families well.