8/14/2019 Oncogenic Viruses Notes

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v-src in Rous sarcoma virus (RSV)

v-src the constitutively active mutant form of c-Src protein

v-src induce cell transformation in the presence of normal c-src proto-oncogene

Viruses incorporated or transduced a normal cellular protooncogene into their genome

Slow-acting retroviruses lack oncogenes. They cause disease by activating expression of c-myc. C-myc isrequired for transcription of many genes that encode cell cycle proteins.

Retroviral promoter and enhancer insertion thus activating the c-myc protooncogene

Single point mutation of the Ras gene

Retroviral oncogenes which are derived from normal cellular genes and have no function for the virus

Gain-of-function mutations in protooncogenes

Loss –of-function mutations in tumor suppressor genes act recessively

Intracellular proteins, such as the p16 cyclin -kinase inhibitor, that regulate or inhibit progressionthrough a specific stage of the cell cycle

Receptors for secreted hormones (e.g., tumorderived growth factor β) that function to inhib it cellproliferation

Checkpoint-control proteins that arrest the cell cycle if DNA is damaged or chromosomes areabnormal

Proteins that promote apoptosis

Enzymes that participate in DNA repair

Familial Adenomatous polypopsis – mutation in the APC gene (adenomatous polypopsis coli) a tumorsuppressor gene-> 100% risk of colorectal cancer

BRCA1 gene-responsible for repairing DNA – risk of breast cancer

Dominant gain-of-function mutations in protooncogenes and recessive loss-of-function mutationsin tumor -suppressor genes are oncogenic.

Among the proteins encoded by proto-oncogenes are positive-acting growth factors and theirreceptors, signal-transduction proteins, transcription factors, and cell-cycle control proteins

(see Figure 24-9 ).

An activating mutation of one of the two alleles of a proto-oncogene converts it to an oncogene,which can induce transformation in cultured cells or cancer in animals.

Activation of a proto-oncogene into an oncogene can occur by point mutation , gene amplification,and gene translocation.

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The first recognized oncogene , v-src, was identified in Rous sarcoma virus , a cancer-causing retrovirus . Retroviral oncogenes arose by transduction of cellular proto-oncogenes intothe viral genome and subsequent mutation .

The first human oncogene to be identified encodes a constitutively active form of Ras, a signal-transduction protein . This oncogene was isolated from a human bladder carcinoma (see Figure

24-4 ).

Slow-acting retroviruses can cause cancer by integrating near a proto-oncogene in such a waythat gene transcription is activated continuously and inappropriately.

Tumor-suppressor genes encode proteins that slow or inhibit progression through a specificstage of the cell cycle ,checkpoint -control proteins that arrest the cell cycle if DNA is damaged orchromosomes are abnormal, receptors for secreted hormones that function to inhibit cellproliferation, proteins that promote apoptosis , and DNA repair enzymes.

Inherited mutations causing retinoblastoma led to the identification of RB, the first tumor-suppressor gene to be recognized.

Inheritance of a single mutant allele of many tumor -suppressor genes (e.g., RB, APC, and BRCA1 ) increases to almost 100 percent the probability that a specific kind of tumorwill develop.

Loss of heterozygosity of tumor -suppressor genes occurs bymitotic recombination or chromosome missegregation