From CellBiology

Tumor Suppressor Protein - p53


The Tumor Suppressor Protein 53 (TP53), is a nuclear phospho-protein found in very low amounts in normal, undamaged cells.
It is composed of a single polypeptide structure with a molecular weight of 53 kDa and contains approximately 393 amino acids.
The TP53 gene is defined as the guardian of the genome, due to its involvement in the regulation of cellular growth & division - prior to recognition of, and response to, DNA damage.

Conversely, it is also the most frequently mutated gene throughout the human genome, whereby, this is identified by accredited journals & researchers - fifty percent of the following cases of cancer are due to the mutation of TP53.
Effortlessly, the gene can be mutated & manipulated into inducing anti-proliferative roles.[1][2][3][4][5]


The TP53 gene is localised on the short arm of chromosome 17 (17p13) and encodes a DNA-binding protein with tumor-suppressive properties.[3]

The composition of the gene is composed of three structural regions with key physiological functions associated with it:

  • The N-terminal region, is comprised of two features:
    • Transcriptional activation domain (amino acids 1-42), is required for transactivation & interacts with various transcription factors.
    • Proline-rich region (amino acids 61-94), is essential for stabilising the integrity of the TP53 gene and also, this region becomes deleted due to mutation of the TP53 gene.[5][6][7]
The structural domains of the TP53 gene.
  • The Central-Core region is localised within the amino acids of 102-292.
    • The specificity role of this region is only for binding to sequence-specific DNA constituents, which are located close to promoters of the TP53 target genes.[5][7]
  • The C-terminal region is comprised of:
    • Nuclear localisation signal sequence (NLS)
    • Oligomerisation domain (amino acids 323-356)
    • 3 nuclear export signal sequence (NES)
    • Regulatory domain (amino acids 360-393)[6][7]


The main role of the TP53 gene, is involved in maintaining the genetic integrity in recognition of, and response to, DNA damage, whereby, it implicates with cell cycle arrest, DNA repair and Programmed Cell Death – Apoptosis.
The effects of DNA damage can be caused by following traumatic stress, such as, exogenous or endogenous agents (e.g. UV or mycotoxins, etc), in which high levels of DNA damage could lead to structural & functional conformation of the TP53 gene, therefore - becoming a mutational strain.[3][8]

  • Throughout a non-stressed normal cell, the half-life of the TP53 gene is relatively short-lived, with approximately 6-20 minutes and is associated with the MDM2 gene - a protein that regulates the inactivity of TP53 gene & constantly targets it for degradation.[4][9][10]
  • When a healthy cell recognises DNA damage, the life-expectancy of the TP53 gene increases, as a result, TP53 & MDM2 is phosphorylated. It then leads to the dissociation of the TP53 gene from the MDM2 and becomes activated to induce post-transcriptional modifications.[1][9]
A schematic drawing of the physiological roles of the TP53 gene.

Once the gene is initiated, it leads to activation of the transcription of the Cdk inhibitor p21 - a cell cycle inhibitor. The p21, blocks the cell-division cycle through inhibiting DNA replication by binding to PCNA (proliferating cell nuclear antigen) and differentiates into two physiological pathways: [11][12]

  • Induction of temporary cell-cycle arrest

The TP53 gene aggregates throughout the cell and suspends the cell cycle pathway at the G1, G2 & S phase - giving the cells breathing time to repair the DNA damage.
Consequently, if repairing of the genome is successful, the cell-cycle resumes its proliferating roles & DNA synthesis, in which, TP53 up-regulates transcription of MDM2 and leads to destruction of TP53, in-order to unblock the cell cycle process.[9]

  • Induction of permanent cell-cycle arrest or initiation of apoptosis

If the DNA damage to the genome is severe or irreparable, it leads to the induction of permanent cell-cycle arrest, as this the only protective mechanical approach to suppress anti-proliferate genes.
The cell cycle arrest can be either senescence, in which, it seems to involve global chromatin changes - which drastically & permanently alter the gene expression or apoptosis, a cascade effect of numerous protein which promotes programmed cell death.

Note: If there are genomic modification to the TP53 gene or overexpression of the gene itself, the gene will become stabilised, as a result, it will prevent itself from being degraded by MDM2 and leads to the activation of apoptosis by APAF1 (Apoptotic protease activating factor 1).[9][13]

Click here for more information about apoptosis.

Historical timeline of the TP53 gene.

Timeline - History


The TP53 gene is vulnerable for genetic mutation, whereby, majority leads to the pathological cases of carcinogenesis.

One of the common pathological cases of mutational TP53 is the Li-Fraumeni Syndrome (LFS). LFS is due to, germline inheritance of the mutational strain of the TP53 gene, in which, with accountable cases of 50-70% that includes sarcomas, breast carcinomas, brain tumors, childhood adrenocortical carcinoma & etc. Subsequently, the patient becomes vulnerable to early onsets of neoplastic transformations.[3][8]

The Central-Core Region in the TP53 gene, is the most vulnerable site for genomic alteration, as a result, the following induction of various type of mechanisms which leads to the mutation of the TP53 gene are:[4]

  • Single-nucleotide substitution - leads to the production of a mutant TP53 gene, which differs from the wildtype protein [8]
  • Lesions that prevents the activation of the TP53[6]
  • Mutation within the TP53 structural domain, in which, if both alleles of TP53 carry loss-of-function mutation, no active p53 can be produced[1]
  • The TP53 protein being transciptionally inactive[6]

Consequently, with the abnormality of the TP53 gene, it leads to unregulated cell proliferation, as a result, the cells with DNA damaged undergoes cellular growth & division unchecked and induces neoplastic transformation.

Current Research

The main areas of research based around the TP53 gene, is the utilisation & recognition of various proteins or enzymes, which may contribute to blocking the cell's signaling pathway of the TP53 mutational gene, from inhibiting anti-proliferative roles.

From the Cell Research Journal, the article MicroRNA-21 targets tumor suppressor genes in invasion and metastasis exemplifies the usage of mir-21, whereby, they are a class of miRNAs that contains small non-coding RNAs which targets protein-coding mRNAs.
It is suggested that the mir-21 may have a role in regulating invasion and metastasis by targeting metastasis-related tumor suppressor genes. Consequently, with further research & studies, the mir-21 functionality may contribute to the downregulation of carcinogenesis and to be used for therapeutic purposes. [8][14][15]


  • Amino Acids: Molecule containing amine functional groups.
  • C-Terminal: End of the amino acid localised by carboxyl group.
  • CDK: (Cyclin-dependent kinase) Enzyme which regulates progression of cell.
  • Cell Cycle: Pathway of the cell's differentiation.
  • Chromosome: Genomic material organised into a structure.
  • Exogenous: Something from the outside environment.
  • Endogenous: Something within the inner compartment of a cell or internal environment.
  • G1 Phase: A stage within the cell cycle.
  • G2 Phase: Final stage of interphase before going into Mitosis.
  • Li-Fraumeni Syndrome: Hereditary disorder - develops anti-proliferative cells in early ages.
  • MDM2 gene: Regulator which, deactivates & degrades the TP53.
  • N-terminal: End of the amino acid localised by amine group.
  • P21: Cell-cycle inhibitor, encoded by TP53.
  • Phosphorylate: Adding the molecular phosphate to certain compounds.
  • Polypeptide: Protein consisting of more than one macromolecular unit.
  • Programmed Cell Death: Cellular degradation of the cell itself.
  • Protein kinase: Enzyme which manipulates other proteins to add molecular phosphate to certain compounds.
  • S Phase: Synthesis stage in the cell cycle.
  • Senescence: Permanent stop for in the cell cycle process.


  1. 1.0 1.1 1.2 Russell, P.J. (2006). iGenetics: A Molecular Approach. (2nd ed.). San Francisco, United States of America: Benjamin Cummings.
  2. Yin, Y., & Shen, W.H. (2008). PTEN: a new guardian of the genome. Oncogene. 27(41), 5443-5453.
  3. 3.0 3.1 3.2 3.3 Barnes, D.M., & Camplejohn, R.S. (1996). P53, Apoptosis, and Breast Cancer. Journal of Mammary Gland Biology and Neoplasia. 1(2), 163-175.
  4. 4.0 4.1 4.2 Szymanska, K., & Hainaut, P. (2003). TP53 and mutations in human cancer. Acta biochimica Polonica. 50(1), 231-238.
  5. 5.0 5.1 5.2 Okorokov, A.L., Sherman, M.B., Plisson, C., Grinkevich, V., Sigmundsson, K., Selivanova, G., Milner, J., & Orlova, E.V. (2006). The structure of p53 tumour suppressor protein reveals the basis for its functional plasticity. The EMBO Journal. 25(21), 5191–5200.
  6. 6.0 6.1 6.2 6.3 Bai, L., & Zhu, W.-G. (2006). p53: Structure, Function and Therapeutic Applications. Journal of Cancer Molecules. 2(4), 141-153.
  7. 7.0 7.1 7.2 May, P., & May, E. (1999). Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene. 18(53), 7621-7636.
  8. 8.0 8.1 8.2 8.3 Olivier, M., Petitjean, A., Marcel, V., Petre, A., Mounawar, M., Plymoth, A., de Fromentel, C.C., & Hainaut, P. (2009). Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Therapy. 16(1), 1–12.
  9. 9.0 9.1 9.2 9.3 Kumar, V., Abbas, A.K., Fausto, N., & Mitchell, R.N. (2007). ROBBINS Basic Pathology. (8th ed.). Philadelphia, United States of America: SAUNDERS ELSEVIER.
  10. Oren, M. (2003). Decision making by p53: life, death and cancer. Cell Death and Differentiation. 10(4), 431-442.
  11. Cooper, G.M. (2002). The Cell: A Molecular Approach. (2nd ed.) Retrieved May 19, 2009, from:
  12. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular Biology of the Cell . (4th ed.) Retrieved May 20, 2009, from:
  13. Hill, M. (2009). 2009 Lecture 18 - Cellbiology. Retrieved May 24, 2009, from Cell Biology Wiki Web site: http://cellbiology.med.unsw.edu.au/cellbiology/index.php?title=2009_Lecture_18
  14. Zhu, S., Wu, H., Wu, F., Nie, D., Sheng, S., & Mo, Y.-Y. (2008). MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. 18(3), 350-359.
  15. Wei, S., Shi-wei, H., Jia-ju, L., Zheng, L., Xiao-lei, F., Xun-bo, J., & Ming-zhen, Y. (2009). Expression of p53 isoforms in renal cell carcinoma. Chinese Medical Journal. 122(8), 921-926.

Lecture Feedback

Lab 6 - "If you've seen differences in the distribution of phenotypes in Tm4 over-expressing B35 cells versus control B35 cells, describe these differences. Formulate a hypothesis with regards to what changes on the molecular level may have occurred due to the over-expression of Tm4 that lead to morphological changes that you have observed"

In the control B35 cells, the individual cellular structures are palpable - displaying morphological differences in their lamellum, showing Fan, Broken Fan, Stumped, Pronged, Stringed or Pygnotic. They also demonstrate variability in their neurite distribution.

In the Tm4 over-expressing B35 cells, they are portray mostly as Pronged shape, in which, they demonstrate more than one neurite extending distally from their soma.

Therefore, the overexpression of Tm4 cells allow them to generate more neurite communication.

Lecture 15 - Cell Cycle

What does "S" stand for in the S phase?

The S stands for synthesis, DNA synthesis.

Lecture 14 - Confocal Microscopy

What are the 2 main forms of generating confocal microscopy?

The two primary forms for generating confocal microscope would be via Laser and Spinning Disc

--Mark Hill 00:19, 30 April 2009 (EST) No, look at the lab page for the answer.

Lecture 10 - Cytoskeleton 1 Intermediate Filaments

The following epithelial skin layers between the Stratum Basale and the Stratum Granulosum is the Stratum Spinosum, whereby that actively synthesises the intermediate filaments, in which they are composed of keratin.

Lecture 8 - Cell Junctions

  • Ng-CAM is defined as Neuron-glia Cell Adhesion Molecule, in which, it is a type of adhesion molecule that associates in binding between the neurons & between neurons and glia.
  • L-CAM is defined as Liver Cell Adhesion Molecule, whereby it appears on non-neural epithelial tissues and it mediates calcium-dependent adhesion in the tissues located in the embryo and in the adult
  • I-CAM is defined as Intercellular Adhesion Molecules, in which, they are members of the family of Cell Adhesion Molecules and the CAMS are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix.

Lecture 7 - Cell Mitochondria

What types of cellular processes require lots of energy from the mitochondria?

The following types of cellular process which requires lots of energy from the mitochondria is the

  • Cellular Respiration Process
  • Cardiac, Skeletal and Smooth Muscle Cellular Process have high levels of mitochondria, in which are packed in between the sarcomeres
  • Tails of the sperm motility requires a lot of energy in which, the mitochondria's are packed near the flagella.
  • Electron Transport Chain
  • Cells export and import
  • Mitochondrial Fusion - in which requires large GTPases

Lecture 5 - Exocytosis

What did you find difficult to understand about exocytosis?

The function of Golgi Apparatus is difficult to understand, do they also pre-determine the functions of proteins or are they just an protein factory, also do they have any connections with nucleus throughout the DNA transcribing into mRNA?

Lecture 4 - Nucleus

  • One Concept That I Found Interesting From The Lecture On The Nucleus

Would be the Functional Compartments within the nucleus, in which, it is composed of two aspects:

    • Cajal Bodies: custer of proteins that comes togther.

What occurs at these sites, is that it is an functional region where the processing of mRNA goes on, whereby small nuclear snRNPs and small nucleolar RNAs assembles together and they are involved in the splicing of the mRNA - therefore they are localised into the interchromatin regions, to become the Cajal Bodies.

    • PML Bodies: also known as promyelocytic Leukaemia Nuclear Bodies or either called PODS, their functions is unknown.

There specific functional domain within the nucleus are separated from the Cajal Bodies, in which, it is thought that they are possible involved in cellular transformation. Alternatively, PML bodies becomes more apparent and assembles together within the cell due to, the cell produces a stress response or either due to DNA damage.

wiki practices

Comparison of the morphological structure
Apoptosis Necrosis
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