Tumor Protein 53

TUMOR PROTEIN 53 (TP53)

Q. 1

About p53 all are true except 

 A

Encodes 53k Da protein

 B

Located on Chr. 17

 C

Arrests cell cycle at GI phase

 D

Wild type p53 is associated with childhood tumors.

Q. 1

About p53 all are true except 

 A

Encodes 53k Da protein

 B

Located on Chr. 17

 C

Arrests cell cycle at GI phase

 D

Wild type p53 is associated with childhood tumors.

Ans. D

Explanation:

Wild type p53 is associated with childhood tumours [Ref: Bobbin’s 8th/e p. 290, 291, 292]

Wild type 53 is the normal (non mutated form of p53).

  • The normal p53 gene is a tumour suppressor gene that prevents the development of tumours.
  • When wild/normal p53 gene undergoes some mutation, it is called the mutant p53 gene.
  • Mutant p53 gene is associated with various human cancers.

– A little over 50% human tumours contain mutation in this gene.

– Homozygous loss of p53 occurs in virtually every type of cancer including carcinomas of the lung, colon and breast.

p53 Guardian of genome

  • p53 gene is located on chromosome 17Q.
  • It is a tumour suppressor gene.
  • “p53 acts as a molecular policemean that prevents the propagation of genetically damaged cell”.

p53 gene product i.e., p53 protein is a DNA binding protein in the nucleus, when called into action, it controls the transcription of several other genes.

  • The major functional activities of the p53 protein are: ?

Activation of temporary cell cycle arrest (quiescence)

p53 induces transcription of p21°, a CDK inhibitor.

– p21 inhibit cyclin D-CDK-4 e complex leading to arrest of cell cycle late in G1 phase. – This allows time for DNA repair (1.

DNA repair

p53 helps in DNA repair not only by allowing time for DNA repair but also by directly inducing the transcription of GADD 45Q (growth arrest and DNA damage).

GADD 45 encodes a protein that is involved in DNA repair.

– If DNA damage is repaired successfully, p53 activates MDM 2 which in turn causes degradation of p53. This MDM-2 induced degradation of p53 causes relieve in cell cycle block.

Triggering of programmed cell death

p53 directs the transcription of several pro-apoptotic genes such as BAX and PUMA (approved name BBC3) and induces apoptosis.

Induction of pennanent cell cycle arrest (quiescent)

p53 can also cause permanent cell cycle arrest.

It is characterized by specific changes in morphology and the exact mechanism is not known.


Q. 2

In a Teritary level Lab it is observed that chronic, increased exposure to ionizing radiation results in damage to cellular DNA. As a consequence, a protein is now absent that would arrest the cell in the G1 phase of the cell cycle. Subsequent to this, the cell is transformed to acquire the property of unregulated growth. The absent protein is most likely the product of which of the following genes?

 A RAS
 B VHL
 C p53
 D MYC
Q. 2

In a Teritary level Lab it is observed that chronic, increased exposure to ionizing radiation results in damage to cellular DNA. As a consequence, a protein is now absent that would arrest the cell in the G1 phase of the cell cycle. Subsequent to this, the cell is transformed to acquire the property of unregulated growth. The absent protein is most likely the product of which of the following genes?

 A RAS
 B VHL
 C p53
 D MYC
Ans. C

Explanation:

p53


Q. 3 False about p53 is:
 A It is present on chromosomes 17
 B It causes cell cycle arrest in G 1
 C 53 KDa
 D Non mutated wild p53 is asssociated with neoplasm in childhood
Q. 3 False about p53 is:
 A It is present on chromosomes 17
 B It causes cell cycle arrest in G 1
 C 53 KDa
 D Non mutated wild p53 is asssociated with neoplasm in childhood
Ans. D

Explanation:

Non mutated wild p53 is asssociated with neoplasm in childhood

Quiz In Between


Q. 4

What is the half-life of p53 protein in normal cells?

 A

20 minutes

 B

60 minutes

 C

12 hours

 D

1 day

Q. 4

What is the half-life of p53 protein in normal cells?

 A

20 minutes

 B

60 minutes

 C

12 hours

 D

1 day

Ans. A

Explanation:

In non stressed, healthy cells, p53 has a short half-life (20 minutes), because of its association with MDM2, a protein that targets it for destruction.
When the cell is stressed, for example by an assault on its DNA, p53 undergoes post-transcriptional modifications that release it from MDM2 and increase its half-life. Unshackled from MDM2, p53 also becomes activated as a transcription factor.
Ref: Robbins 8th edition Chapter 7.

 


Q. 5

Which of the following statements is not correct regarding p53 gene?

 A

Located on chromosome 17

 B

Arrests cell cycle at Gl phase

 C

Is a 53 kDa protein

 D

Wild type is associated with tumors

Q. 5

Which of the following statements is not correct regarding p53 gene?

 A

Located on chromosome 17

 B

Arrests cell cycle at Gl phase

 C

Is a 53 kDa protein

 D

Wild type is associated with tumors

Ans. D

Explanation:

Wild type of p53 gene refers to the Normal (Non-mutated) form of p53 gene.
The wild type of p53 gene (Normal/Non-mutated) is a tumor suppressor gene that maintains the genetic integrity of cells and prevents the development of tumors.
It is the mutated form of p53 gene (and not the wild type) that is associated with tumors.
 
Ref: Harrison’s Principles of Internal Medicine, 17th Edition, Pages 499, 500; Cancer: Principles and Practice of Oncology By De vita, 6th Edition, Page 19; Robbin’s Illustrated Pathology, 7th Edition, Page 302; Textbook of Pathology By Harsh Mohan, 5th Edition, Pages 2216-17

Q. 6

‘Policemen gene’ or ‘Guardian gene’ is the name given to?

 A

Myc

 B

Meu

 C

P53

 D

Abl

Q. 6

‘Policemen gene’ or ‘Guardian gene’ is the name given to?

 A

Myc

 B

Meu

 C

P53

 D

Abl

Ans. C

Explanation:

p53 acts as a ‘molecular policemen’ that prevents the propagation of genetically damaged cells. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer.

As such, p53 has been described as “the guardian of the genome” because of its role in conserving stability by preventing genome mutation.

Ref: Robbins Pathology, 7th Ed, page 302

Quiz In Between


Q. 7

Which of the following statement is NOT true about p53 protein?

 A

It is present on chromosomes 17

 B

It causes cell cycle arrest in G1

 C

53 KDa

 D

Non mutated wild p53 is associated with neoplasm in childhood

Q. 7

Which of the following statement is NOT true about p53 protein?

 A

It is present on chromosomes 17

 B

It causes cell cycle arrest in G1

 C

53 KDa

 D

Non mutated wild p53 is associated with neoplasm in childhood

Ans. D

Explanation:

The tumor suppressor p53, a protein of apparent MW 53 kDa.

The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13).

When DNA Is damaged, the p53 protein accumulates in cells.

It first arrests the cell cycle (at the G1 phase) to allow the DNA to be repaired before it is replicated.

A cell with damaged DNA that cannot be repaired is directed by p53 to either enter senescence or undergo apoptosis.

In view of these activities, p53 has been called the ‘guardian of the genome’. 

With homozygous loss of the TP53 gene, DNA damage goes unrepaired, mutations become fixed in dividing cells, and the cell turns to malignant transformation.
 
Ref: Robbins Basic Pathology By Vinay Kumar, Abul K. Abbas, Nelson Fausto, Richard Mitchell, 2012, Page 20, 185-187

Q. 8

Which of the following is known as the guardian of the genome?

 A

VEGFR-2

 B

p53

 C

Mdm2

 D

4ATM

Q. 8

Which of the following is known as the guardian of the genome?

 A

VEGFR-2

 B

p53

 C

Mdm2

 D

4ATM

Ans. B

Explanation:

Due to its critical importance in maintaining genetic stability p53 is called the “gatekeeper” or “guardian” of the genome.
 
The tumor suppressor protein p53 is a key regulator, of the cellular response to geno-toxic damage, and thus plays a pivotal role in preventing cancer formation. Once DNA damage has been incurred, p53 can elicit several different responses to either correct the errors or destroy the damaged cell. 
 
3 Important actions: 
 
1. p53 can induce G1 cell cycle arrest, which stops the cell from dividing and allows time to repair the damage before the DNA is replicated. 
 
2. p53 can activate DNA repair proteins to drive the repair of damaged DNA. 
 
3. As a last resort, p53 can induce damaged cells to undergo programmed cell death (apoptosis), thereby eliminating damaged and potentially dangerous cells at risk for neoplastic transformation. 
 
Ref: Cancer Genome and Tumor Microenvironment, By Andrei Thomas-Tikhonenko, 2010, Page, 190

Q. 9

Regarding oncogenesis –

 A

Topoisomerase causes breaks in strands

 B

P53 is the most common oncogene mutation causing malignancy in humans

 C

At G2-M-phase there is loss of inhibitors controlling cell cycle

 D

All options are correct

Q. 9

Regarding oncogenesis –

 A

Topoisomerase causes breaks in strands

 B

P53 is the most common oncogene mutation causing malignancy in humans

 C

At G2-M-phase there is loss of inhibitors controlling cell cycle

 D

All options are correct

Ans. D

Explanation:

 

o p53 gene is located on chromosome 17p13 and it is the most common target for genetic alteration in human tumors. A little over 50% human tumors contain mutation in this gene.

o DNA topoisomerase bind tightly to DNA double helix and make transient breaks in both strands.

o Telomerase activity and maintenance of Telomer length are essential for maintenance of relicative potential in tumor cells —> Decrease of telomerase activity cause antitumor effects

o GIS and G2M are cell cycle check point and defect in cell cycle check point component is a major cause of genetic instability in cancer cells.

Quiz In Between


Q. 10

Increased susceptibility to breast cancer is likely to be associated with a mutation in the following gene-      

 A

p53

 B

BRCA-1

 C

Retinoblastoma

 D

a and b

Q. 10

Increased susceptibility to breast cancer is likely to be associated with a mutation in the following gene-      

 A

p53

 B

BRCA-1

 C

Retinoblastoma

 D

a and b

Ans. D

Explanation:

 

o Genetic mutations associated with breast cancer are of two types‑

(i)      Germline mutations (inherited mutations)

o Involved in familial cases of breast cancer

(ii)    Somatic mutations (acquired mutation)

o Involved in sporadic cases of breast cancer

o Tumour suppressor genes involved in Breast cancer

(i) Genes involved in germline mutations (cause familial Breast Ca)

(a)  BRCA-1 and BRCA-2 –> Causes familial breast and ovary Ca

(b)  p53 —> (Li Fraumeni syndrome) — There is increased susceptibility to Ca breast, colon, leukemia, Sarcomas, brain tumours.

(ii) Genes involved in Somatic mutation (cause spordic breast cancer or primary breast cancer) —-> p53

o So p53 gene is involved in both germline mutation and somatic mutation causing breast cancer. Where as BRCA-1 is involved only in germline mutation


Q. 11

Which of the following mutations in a tumour suppressor agent causes breast carcinoma?

 A

p43

 B

p53

 C

p73

 D

p83

Q. 11

Which of the following mutations in a tumour suppressor agent causes breast carcinoma?

 A

p43

 B

p53

 C

p73

 D

p83

Ans. B

Explanation:

Q. 12

Which of the following is known as the “guardian of the genome”?

 A

p53

 B

Mdm2

 C

p14

 D

ATM

Q. 12

Which of the following is known as the “guardian of the genome”?

 A

p53

 B

Mdm2

 C

p14

 D

ATM

Ans. A

Explanation:

 

p53; Guardian of genome

o p53 is a tumor suppressor gene.

o p53 gene is located on chromosome 17.

o p53 acts as molecular policeman that prevents the propagation of genetically damage cell.

o p53 gene product, i.e. p53 protein is a DNA binding protein in the nucleus, when called into action, it controls the transcription of several other genes.

o The major functional activities of the p53 protein are cell cycle arrest and initiation of apoptosis in response to DNA damage.

o When there is DNA damage due to irradiation, UV light or mutagenic chemicals, there is rapid increase in p53

levels.

Quiz In Between


Q. 13

The following statements are true about Tumour Suppressor Gene p53 except –

 A

It regulates cetain genes involved in cell cycle regulation

 B

Its increased levels can induce apoptosis

 C

Its activity in the cells decreases following UV irradiation and stimulates cell cycle

 D

Mutations of the p53 gene are the most common genetic alteration seen in human cancer

Q. 13

The following statements are true about Tumour Suppressor Gene p53 except –

 A

It regulates cetain genes involved in cell cycle regulation

 B

Its increased levels can induce apoptosis

 C

Its activity in the cells decreases following UV irradiation and stimulates cell cycle

 D

Mutations of the p53 gene are the most common genetic alteration seen in human cancer

Ans. C

Explanation:

Q. 14

True statements about P53 gene are all except

 A

Arrest cell cycle at GI Phase

 B

Product is 53 KD protein

 C

Located on chromose 17

 D

Wild/non-mutated form is associated with in­creased risk of childhood tumors.

Q. 14

True statements about P53 gene are all except

 A

Arrest cell cycle at GI Phase

 B

Product is 53 KD protein

 C

Located on chromose 17

 D

Wild/non-mutated form is associated with in­creased risk of childhood tumors.

Ans. D

Explanation:

 

It is mutated form (not non mutated form) of p53 which is associated with increased risk of tumors.

o p53 gene is a tumor suppressor gene and non-mutated form of this gene prevent development of malignancy by :

(i)   Causing cell cycle arrest in late GI phase

(ii)   Inducing apoptosis

(iii)  Helping in DNA repair

o Mutation in p53 gene causes inactivation of p53 gene and abolishen of above function that results in uncontrolled proliferation of cells and malignant transformation.

o Mutation in p53 gene is the most common genetic alteration found in human Cancer.

o The name p53 is in reference to its apparent molecular mass; it runs as a 53 kilodalton (Kda) protein on SDS-page. But based on calculations from its amino acid residues, p53 ‘s mass is actually only 43.7 K Da.

 

o p53 prevents neoplastic transformation by three interlocking mechanisms :

1.  Activation of temporary cell cycle arrest (quiescence)

o It is considered as the primordial response to DNA damage.

o p53 causes arrest in late GI through p2 I .

o This is temporary arrest that gives the cell “breathing time” to repair DNA damage.

o After DNA repair, cell cycle block is relieved by MDM-3 which degrades p53.

2.  Induction of permanent cell cycle arrest (senescence)

o p53 induced sencence is a permanent cell cycle arrest characterized by specific changes in morphology and gene expression that differentiate it from quiescence (temporary or reversible cycle arrest).

o The mechanisms of senscence is unknown, but involve epigenetic changes that result in the formation of heterochromatin at different loci throughout the genome.

3.  Triggering of programmed cell death

o p53 directs the transcription of several pro-apoptotic genes such as BAX and PUMA (approved name BBC3) and induces apoptosis.

o It has been shown that p53 activates transcription of the mir 34 family of micro RNAs (miRNAs),mir 34a.

o mir34 inhibits translation of anti-apoptotic genes such as BCL2 (there by induce apoptosis) and pro-proliferative genes such as cyclins (there by prevent proliferation) p53 induce apoptosis and prevent proliferation through mir34.


Q. 15

True about p53 –

 A

Tumor suppressor gene

 B

Protooncogene

 C

Proapoptotic

 D

a and c

Q. 15

True about p53 –

 A

Tumor suppressor gene

 B

Protooncogene

 C

Proapoptotic

 D

a and c

Ans. D

Explanation:

 

o p 53 is a tumor suppressor gene and it is a proapoptotic factor, i.e. it promotes apoptosis if repair of DNA damage is unsuccessful at G1 arrest.

o The name p53 is in reference to its apparent molecular mass; it runs as a 53 kilodalton (Kda) protein on SDS-page. But based on calculations from its amino acid residues, p53 ‘s mass is actually only 43.7 K Da.

Quiz In Between


Q. 16

False about p53 is –

 A

It is present on chromosomes 17

 B

It cvauses cell cylce arrest in G1

 C

53 KDa

 D

Non mutated wild p53 is associated with neoplasm in childhood

Q. 16

False about p53 is –

 A

It is present on chromosomes 17

 B

It cvauses cell cylce arrest in G1

 C

53 KDa

 D

Non mutated wild p53 is associated with neoplasm in childhood

Ans. D

Explanation:

Ans. is ‘d’ i.e., Non mutated wild p53 is associated with neoplasm in childhood

It is mutated form (not non mutated form) of p53 which is associated with increased risk of tumors.

o p53 gene is a tumor suppressor gene and non-mutated form of this gene prevent development of malignancy by :

(i)       Causing cell cycle arrest in late GI phase

(ii)     Inducing apoptosis

(iii)      Helping in DNA repair

o Mutation in p53 gene causes inactivation of p53 gene and abolishen of above function that results in uncontrolled proliferation of cells and malignant transformation.

o Mutation in p53 gene is the most common genetic alteration found in human Cancer.

o The name p53 is in reference to its apparent molecular mass; it runs as a 53 kilodalton (Kda) protein on SDS-page. But based on calculations from its amino acid residues, p53’s mass is actually only 43.7 K Da.


Q. 17

The tumor suppressor gene P53 induces cell arrest at-

 A

M phase

 B

S – G2 phase

 C

G1 – S phase

 D

Go – phase

Q. 17

The tumor suppressor gene P53 induces cell arrest at-

 A

M phase

 B

S – G2 phase

 C

G1 – S phase

 D

Go – phase

Ans. C

Explanation:

Ans. is ‘c’ i.e., G1 – S phase


Q. 18

In Breast cancer following are expressed: 

 A

HER2/neu

 B

P53

 C

B RCA1

 D

All

Q. 18

In Breast cancer following are expressed: 

 A

HER2/neu

 B

P53

 C

B RCA1

 D

All

Ans. D

Explanation:

Ans. is ‘a’, ‘b’ & ‘c’ i.e. HER2/neu, P53 & BRCA1

Quiz In Between



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