2. Content
Introduction
1. The retinoblastoma tumor suppressor gene.
2. The Tp53 tumor suppressor gene.
3. pAPC tumor suppressor gene.
4. pBRAC1 and pBRAC2 tumor suppressor gene.
References.
3. Introduction
• Occasionally, dividing and differentiating cell deviate from
their normal genetic program and give rise to tissue masses
called tumors.
• Normal cell contained gene product that have the ability to
suppress uncontrolled cell proliferation characteristics of
cancer cell is termed as tumor suppressor gene.
4. 1. Retinoblastoma tumor suppressor gene
• The RB gene was cloned in 1986. It spans 180 kb of DNA and
encodes 4.7-kb mRNA that is translated to produce the 928-amino
acid nuclear phosphoprotein, pRB.
• pRB is involved in regulating the cell cycle at the G1-to-S
checkpoint.
• pRB is found in a complex with transcription factor E2F and,
when pRB is unphosphorylated, the activity of E2F is inhibited.
• Then, when pRB becomes phosphorylated, the inhibition of E2F
activity is removed and the now-active transcription factor turns
on the transcription of genes for DNA synthesis.
5. • Retinoblastoma develops during the period from birth to age 4
years and is the most common eye tumor in children.
• By laser therapy or by radiation therapy more than 90% of the eye
tumors can be permanently destroyed.
• There are two forms of retinoblastoma: In sporadic retinoblastoma
(60% of cases) and In hereditary retinoblastoma (40% of cases).
• Retinoblastoma is a cancer caused by two mutational events, One
mutation is inherited the germinal cells and the second occurs in
somatic cells.
• Knudson’s two-hit mutational model, as exemplified by
retinoblastoma.
9. 2. The TP53 Tumor Suppressor Gene.
• The tumor suppressor gene TP53 encodes a protein of
molecular weight 53 kDa called p53.
• When both alleles are mutated, TP53 may be involved in the
development of perhaps 50% of all human cancers, including
breast, brain, liver, lung, colorectal, bladder, and blood cancers.
• Function of p53. The 393-amino acid p53 tumor suppressor
protein is a transcription factor that is regulated by
phosphorylation and by its interaction with another
phosphoprotein, the negative regulator Mdm2.
10. • In a normal cell, both proteins are unphosphorylated, which
allows them to bind together.
• Mdm2 stimulates degradation of p53, and as a result, the
amount of p53 in the cell is low.
• When DNA damage occurs, p53 initiates a cascade of events
leading to arrest in .
12. 3. pAPC
• The 310-kilodalton pAPC protein was discovered through the
study of adenomatous polyposis coli, an inherited condition that
often leads to colorectal cancer.
• This large protein, plays a key role in regulating the renewal of
cells in the lining, or epithelium, of the large intestine.
• pAPC controls the proliferation and differentiation of cells in
the epithelium of the intestine.
• When pAPC function is lost, the cells that generate the finger
like projections on the intestinal epithelium remain in an
undifferentiated state.
14. 4. pBRCA1 and pBRCA2
• BRCA1 was mapped to chromosome 17 in 1990 and isolated in
1994.
• And BRCA2 was mapped to chromosome 13 in 1994 and isolated
in 1995.
• Both pBRCA1 and pBRCA2 carry out important function within
the cells.
• Mutation in both the genes account for about 7 percent of all the
case in breast cancer and 10 percent in ovarian cancer.