Tumor suppressors, the products of tumor suppressor genes (also known as anti-oncogenes), transduce negative cell growth regulation signals such as those involved in cell cycle arrest and apoptosis. Tumor suppressor genes can help the cell respond to mutations before dividing and passing on altered DNA. Mutations to tumor suppressor genes can result in abnormal cell growth and tumor formation. For instance, certain inherited mutations, such as BRCA1 and BRCA2, are linked to a higher risk of breast cancer. p53 gene mutation (absent or impaired) is a common change in cancerous cells. In this article, CUSABIO list several tumor suppressors which are popular with customers, click to see all the related targets and research reagents of them.
Here, we enumerate four tumor suppressors which are most popular with customers.
p53, also known as TP53, is a tumor suppressor gene that encodes for protein involved in cell regulation [1]. This gene is mapped on the 17th chromosome and functions by binding to a specific region DNA, which stimulates production of the p21 protein. Then p21 protein subsequently inhibits uncontrolled cell division and related tumors. In addition to the role as tumor suppressor, p53 is also essential to the control of metabolism and ferroptosis (iron- and lipid-peroxide-mediated cell death) [2].
p21, also known as cyclin-dependent kinase inhibitor 1, is encoded by the CDKN1A gene located on chromosome 6 (6p21.2) in humans. This protein is an inhibitor of cyclin-dependent kinases that are required for cell cycle progression. In many cell types, p53-mediated growth inhibition is dependent on induction of p21, which represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest [3]. Failure of mutant p53 proteins to transactivate p21 may lead to uncontrolled proliferation.
p27, also called Cyclin-dependent kinase inhibitor 1B (CDKN1B), is an enzyme inhibitor that binds to and inhibits the activation of cyclin E/CDK2 or cyclin D/CDK4 complexes in order to regulate cell cycle progression at G1. Within cells, p27 is located primarily in the nucleus, where it plays a critical role in controlling cell growth and division [4].
EP300, also called histone acetyltransferase p300 or P300, is an enzyme that regulates transcription of genes via chromatin remodeling by allowing histone proteins to wrap DNA less tightly. This enzyme plays an essential role in regulating cell growth and division, prompting cells to mature and assume specialized functions (differentiate), and preventing the growth of cancerous tumors. The p300 protein appears to plays a crucial role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls the terminal differentiation of intestinal epithelium cells [5].
References
[1] Humpton TJ, Vousden KH. Regulation of cellular metabolism and hypoxia by p53 [J]. Cold Spring Harb Perspect Med. 2016, 6(7):211–30.
[2] Gnanapradeepan K, Basu S, Barnoud T et al. The p53 Tumor Suppressor in the Control of Metabolism and Ferroptosis [J]. Front Endocrinol (Lausanne). 2018, 11; 9: 124.
[3] Elbendary AA, Cirisano FD, Evans AC Jr et al. Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells [J]. Clin Cancer Res. 1996, 2(9): 1571-5.
[4] Molatore, Sara (2010). [Progress in Brain Research] Neuroendocrinology - Pathological Situations and Diseases Volume 182 || The MENX Syndrome and p27: Relationships with Multiple Endocrine Neoplasia. , (), 295–320.
[5] Sneha, P. (2018). [Advances in Protein Chemistry and Structural Biology] Protein-Protein Interactions in Human Disease, Part A Volume 110 || Probing the Protein–Protein Interaction Network of Proteins Causing Maturity Onset Diabetes of the Young. , (), 167-202.
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