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p53, also known as Tumor protein P53, cellular tumor antigen p53, or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence TP53 is classified as a tumor suppressor gene.
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.
p73 is a protein related to the p53 tumor protein. Because of its structural resemblance to p53, it has also been considered a tumor suppressor. It is involved in cell cycle regulation, and induction of apoptosis. Like p53, p73 is characterized by the presence of different isoforms of the protein. This is explained by splice variants, and an alternative promoter in the DNA sequence.
Mouse double minute 2 homolog (MDM2) also known as E3 ubiquitin-protein ligase Mdm2 is a protein that in humans is encoded by the MDM2 gene. Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.
p14ARF is an alternate reading frame protein product of the CDKN2A locus. p14ARF is induced in response to elevated mitogenic stimulation, such as aberrant growth signaling from MYC and Ras (protein). It accumulates mainly in the nucleolus where it forms stable complexes with NPM or Mdm2. These interactions allow p14ARF to act as a tumor suppressor by inhibiting ribosome biogenesis or initiating p53-dependent cell cycle arrest and apoptosis, respectively. p14ARF is an atypical protein, in terms of its transcription, its amino acid composition, and its degradation: it is transcribed in an alternate reading frame of a different protein, it is highly basic, and it is polyubiquinated at the N-terminus.
Adenovirus E1B protein usually refers to one of two proteins transcribed from the E1B gene of the adenovirus: a 55kDa protein and a 19kDa protein. These two proteins are needed to block apoptosis in adenovirus-infected cells. E1B proteins work to prevent apoptosis that is induced by the small adenovirus E1A protein, which stabilizes p53, a tumor suppressor.
p16, is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase, thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16, accelerating the cell cycle and resulting in many types of cancer.
Protein inhibitor of activated STAT (PIAS), also known as E3 SUMO-protein ligase PIAS, is a protein that regulates transcription in mammals. PIAS proteins act as transcriptional co-regulators with at least 60 different proteins in order to either activate or repress transcription. The transcription factors STAT, NF-κB, p73, and p53 are among the many proteins that PIAS interacts with.
CHEK2 is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers.
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.
Inhibitor of growth protein 1 is a protein that in humans is encoded by the ING1 gene.
Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. Multiple transcript variants encoding different isoforms have been found for this gene.
Cyclin-dependent kinases regulatory subunit 2 is a protein that in humans is encoded by the CKS2 gene.
Inhibitor of growth protein 2 is a protein that in humans is encoded by the ING2 gene.
Large tumor suppressor kinase 2 (LATS2) is an enzyme that in humans is encoded by the LATS2 gene.
Dual specificity protein phosphatase CDC14B is an enzyme that in humans is encoded by the CDC14B gene.
WRAP53 is a gene implicated in cancer development. The name was coined in 2009 to describe the dual role of this gene, encoding both an antisense RNA that regulates the p53 tumor suppressor and a protein involved in DNA repair, telomere elongation and maintenance of nuclear organelles Cajal bodies.
Human protein 53 intron 1 (Hp53int1) is a protein encoded by the Hp53int1 gene in humans.
References
- ↑ Levrero M, De Laurenzi V, Costanzo A, Gong J, Wang JY, Melino G (May 2000). "The p53/p63/p73 family of transcription factors: overlapping and distinct functions". Journal of Cell Science. 113 ( Pt 10) (10): 1661–1670. doi: 10.1242/jcs.113.10.1661 . PMID 10769197.
- ↑ Finch CE (2007). The biology of human longevity: inflammation, nutrition, and aging in the evolution of lifespans. Academic Press. pp. 350–. ISBN 978-0-12-373657-4 . Retrieved 23 December 2010.
- ↑ Chen S, Moroi Y, Urabe K, Takeuchi S, Kido M, Hayashida S, et al. (August 2008). "Differential expression of two new members of the p53 family, p63 and p73, in extramammary Paget's disease". Clinical and Experimental Dermatology. 33 (5): 634–640. doi:10.1111/j.1365-2230.2008.02851.x. PMID 18627398. S2CID 19207163.
- ↑ Nedelcu AM, Tan C (December 2007). "Early diversification and complex evolutionary history of the p53 tumor suppressor gene family". Development Genes and Evolution. 217 (11–12): 801–806. doi:10.1007/s00427-007-0185-9. PMID 17924139. S2CID 7794806.
- ↑ Pankow S, Bamberger C (September 2007). Rutherford S (ed.). "The p53 tumor suppressor-like protein nvp63 mediates selective germ cell death in the sea anemone Nematostella vectensis". PLOS ONE. 2 (9): e782. Bibcode:2007PLoSO...2..782P. doi: 10.1371/journal.pone.0000782 . PMC 1964547 . PMID 17848985.
- ↑ Rutkowski R, Hofmann K, Gartner A (July 2010). "Phylogeny and function of the invertebrate p53 superfamily". Cold Spring Harbor Perspectives in Biology. 2 (7): a001131. doi:10.1101/cshperspect.a001131. PMC 2890203 . PMID 20595397.
- 1 2 3 Belyi VA, Ak P, Markert E, Wang H, Hu W, Puzio-Kuter A, Levine AJ (June 2010). "The origins and evolution of the p53 family of genes". Cold Spring Harbor Perspectives in Biology. 2 (6): a001198. doi:10.1101/cshperspect.a001198. PMC 2869528 . PMID 20516129.
- ↑ Levine AJ (August 2020). "p53: 800 million years of evolution and 40 years of discovery". Nature Reviews. Cancer. 20 (8): 471–480. doi:10.1038/s41568-020-0262-1. PMID 32404993.