Tumor Protein 53

TUMOR PROTEIN 53 (TP53)


TUMOR PROTEIN 53/TP53

INTRODUCTION:

  • One among “Tumor suppressor gene”.
  • A Phosphoprotein, barely detectable in nucleus of normal cells.
  • Also referred to as “Molecular policeman”/“Guardian angel of genome” 
    • Due to its protective role in cell cycle.
  • Hallmarks of cancer.
  • In non-stressed, healthy cells has short half-life~20 mins
    • Due to its association with MDM2.
    • MDM2 – Negative regulator of p53 tumor suppressor gene.

STRUCTURE:

  • Located on chromosome 17
  • Encodes d on gene TP53 coding 53k Da protein
  • Has seven domains.

FUNCTIONS:

1. Acts as “Tumor suppressor gene”.

  • Anti-cancer effects due to,
    • Enhances DNA repair, thus preventing mutations.
    • Activates quiescence (temporary cell cycle arrest).
    • Induces senescence (permanent cell cycle arrest).
    • Promotes apoptosis of genetically defective cells.

2. Effects of p53 on cell cycle:

  • Arrests cell cycle in G1phase by inhibiting Cyclin-Dependent Kinase (CDK).
    • Damaged DNA repairs during this time.
    • Normally when DNA damage is repaired by GADD45, p53 destructs itself & relieves cell cycle block.
  • If DNA is unrepaired, p53 along with activated BAX & BAK gene induces apoptosis.
    • Also induces senescence through LINC RNA.

3. Effects of p53 on cell repair:

  • On cell stress/injury,

DNA assaulted due to anoxia/inappropriate oncoprotein activity

DNA damage sensed by (ATM & ATR) protein kinases

Kinases phosphorylate p53 & liberate it from MDM2.

p53 accumulates & suppresses neoplastic transformation.

EFFECTS OF p53 MUTATION:

  • No cell cycle arrest.
  • No DNA repair.
  • Limitless replication leads to cancer.
  • Increases susceptibility to cancers 
    • Li-Fraumeni syndrome.
  • HPV encodes protein E6 binding to p53 thus, inhibiting its action.

Exam Important

  • p53 encodes 53k Da protein
  • p53 is located on Chr. 17
  • p53 arrests cell cycle at GI phase
  • Half-life of p53 protein in normal cells is 20 minutes
  • “Policemen gene’ or ‘Guardian gene’ is the name given to P53
  • P53 is the most common oncogene mutation causing malignancy in humans
Don’t Forget to Solve all the previous Year Question asked on TUMOR PROTEIN 53 (TP53)

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