What is the Difference Between P53 and P21

The key difference between p53 and p21 is that p53 arrests the cell growth by holding the cell cycle at the G1/S regulation point upon detecting DNA damage, while p21 binds to G1-S/CDK complexes upon induction by p53 and inhibits the activity of CDK complexes.

DNA repair is the process by which a cell collectively identifies and corrects the damage in DNA molecules. Many of these DNA damages structurally affect the DNA molecule. This can alter the cell’s ability to transcribe important genes, eventually leading to lethal diseases such as cancers.  DNA damages often activate the p53-p21 pathway and cause G1 phase arrest in the cells. p53 and p21 are two important tumor suppressor proteins.

CONTENTS

1. Overview and Key Difference
2. What is P53 
3. What is P21
4. Similarities – P53 and P21
5. P53 vs P21 in Tabular Form
6. Summary – P53 vs P21

What is P53?

P53 is a tumor suppressor protein that arrests cell growth by holding the cell cycle at the G1/S regulation point upon detecting DNA damage. It is also the guardian of the genome. This homolog protein is crucial in multicellular vertebrates because it prevents cancer formation. In addition, P53 conserves the stability of the genome by preventing genome mutation. Hence, P53 is considered a tumor suppressor. This name was first suggested in 1979 based on the molecular mass of p53.

Figure 01: P53

The SDS-PAGE analysis indicates that the p53 is a 53 kilodalton (kDa) protein. Moreover, the p53 gene is the most frequently mutated gene in human cancer. This suggests the crucial role p53 plays in preventing cancer formation. P53 perform many functions. It activates DNA repair proteins, arrests cell growth by holding the cell cycle at the G1/S regulation point. It also initiates apoptosis and is essential for senescence response to short telomeres. Furthermore, induction of p21 by p53 following DNA damage, which inhibits both Cdk4 and Cdk2 activities, can arrest the cell cycle at the G/S regulation point.

What is P21?

P21 is a tumor suppressor protein and a CDK interacting protein that is capable of binding to G1-S/CDK complexes upon induction by p53. Once bound, it inhibits the activity of CDK complexes. It is also known as a cyclin-dependent kinase inhibitor. This is because it is capable of inhibiting all cyclin/CDK complexes. Upon induction by p53, p21 (CIPI/WAF1) binds and inhibits the cyclin-CDK1, CDK2, CDK4/6 complexes. Thus, it functions as a regulator of cell cycle progression at G1/S phase during DNA damage.

Figure 02: P21

Moreover, p21 interacts with proliferating cell nuclear antigen (PCNA) and inhibits it. In this way, p21 acts as an effective inhibitor of DNA synthesis at the S phase. However, it permits nucleotide excision repair in S phase. Furthermore, this protein was reported to be cleaved by caspases like CASP-3, which leads to a dramatic activation of CDK2 again and thus inhibits apoptosis.

What are the Similarities Between P53 and P21?

  • P53 and P21are two important tumor suppressor proteins.
  • Both are small molecular weighted proteins.
  • These proteins are involved in the p53-p21 pathway.
  • Both proteins are very important for the G1 phase arrest of the cell cycle during DNA damage.
  • Both proteins are capable of preventing cancer formation.

What is the Difference Between P53 and P21?

P53 is a tumor suppressor protein that arrests the cell growth by holding the cell cycle at the G1/S regulation point upon detecting DNA damage, while p21 is a tumor suppressor protein and a CDK interacting protein that is capable of binding to G1-S/CDK complexes and inhibiting the activity of CDK complexes upon induction by p53. So, this is the key difference between p53 and p21. Furthermore, P53 initiates apoptosis if the DNA damages are irreparable but, p21 inhibits apoptosis due to cleavage by caspases.

The below infographic lists the differences between p53 and p21 in tabular form for side by side comparison.

Summary – P53 vs P21

DNA damages often activate the p53-p21 pathway and cause G1 phase arrest of the cell cycle. This process is very important for controlling cancer formation. P53 and p21 are two important tumor suppressor proteins in this pathway. P53 is a protein that arrests the cell growth by holding the cell cycle at the G1/S regulation point upon detecting DNA damage, while p21 is a protein that is capable of binding to G1-S/CDK complexes upon induction by p53 and inhibiting the activity of CDK complexes. Thus, this is the summary of the difference between p53 and p21.