TUMOR SUPRESSOR GENES
, Protooncogenes Type of mechanism Protein Oncogenic mutation Remarks
Intracellular proteins. Point mutations. Rb protein The point mutation may lead to a Present in 13th chromosome, The 180 kb Rb gene encodes
Deletions (truncated Rb (Gatekeepers). modified Rb protein that can no 110 kDa nuclear protein called pRb.
protein). longer bind to E2F and inhibit it Normally, Rb phosphorylation by Cyclin D1-Cdk 4 kinase
effectively. frees E2F elongation factor from Rb proteins and allows
Moreover, similarly a truncated continuation of cell cycle (G1 phase to S transition). Thus,
Rb protein also results in Rb protein acts as a repressor of cell cycle by binding to
ineffective binding of Rb protein E2F factor and preventing cell from progressing from G1 to
to E2F. S phase.
Loss of Rb protein results in continual expression of E2F
protein and this results in loss of control of passage from G1
to S phase.
Loss of Rb protein causes retinoblastoma.
There are two types of retinoblastomas.
Sporadic retinoblastoma.
Hereditary retinoblastoma – It is an autosomal
dominant trait.
Binding of viral Rb protein Viral oncoprotein binds to normal E7 protein of Human Papilloma Virus inactivates Rb by
oncoprotein. (Gatekeepers). E3F factor and change the binding to it.
protein structurally thus making it Large T-antigen of SV-40 Polyoma virus binds and
impossible to bind to E2F. inactivates Rb.
E1B protein of Adenovirus also binds to Rb and inactivates
it.
Gene deletion. p16 protein p16 binds to Cyclin D1-Cdk 4 kinase and keeps it in an
Inactivation by (Gatekeepers). inactive form. This prevents subsequent phosphorylation of
hypermethylation of its Rb protein and release of E2F factor.
promoter region. Loss of p16 results in constitutively expressed Cyclin D1-
Cdk 4 kinase and loss of control of passage from G1 to S
phase.
Gene deletion. Smad proteins These are components of TGF- β signalling pathway. Loss
(Gatekeepers). of these proteins inhibits TGF- β pathway and thus
contribute to cell proliferation.
The end product of TGF- β pathway are p15 protein and
PAI-1.
p15 protein is a G1 cyclin kinase inhibitor. It displaces p27
from cyclin D-Cdk 4 complex (this inactivates cyclin D-Cdk 4
complex) and this free p27 attaches itself to Cyclin E-Cdk 2
complex (This inhibits the Cyclin E-Cdk 2 complex). This
, Protooncogenes Type of mechanism Protein Oncogenic mutation Remarks
Intracellular proteins. Point mutations. Rb protein The point mutation may lead to a Present in 13th chromosome, The 180 kb Rb gene encodes
Deletions (truncated Rb (Gatekeepers). modified Rb protein that can no 110 kDa nuclear protein called pRb.
protein). longer bind to E2F and inhibit it Normally, Rb phosphorylation by Cyclin D1-Cdk 4 kinase
effectively. frees E2F elongation factor from Rb proteins and allows
Moreover, similarly a truncated continuation of cell cycle (G1 phase to S transition). Thus,
Rb protein also results in Rb protein acts as a repressor of cell cycle by binding to
ineffective binding of Rb protein E2F factor and preventing cell from progressing from G1 to
to E2F. S phase.
Loss of Rb protein results in continual expression of E2F
protein and this results in loss of control of passage from G1
to S phase.
Loss of Rb protein causes retinoblastoma.
There are two types of retinoblastomas.
Sporadic retinoblastoma.
Hereditary retinoblastoma – It is an autosomal
dominant trait.
Binding of viral Rb protein Viral oncoprotein binds to normal E7 protein of Human Papilloma Virus inactivates Rb by
oncoprotein. (Gatekeepers). E3F factor and change the binding to it.
protein structurally thus making it Large T-antigen of SV-40 Polyoma virus binds and
impossible to bind to E2F. inactivates Rb.
E1B protein of Adenovirus also binds to Rb and inactivates
it.
Gene deletion. p16 protein p16 binds to Cyclin D1-Cdk 4 kinase and keeps it in an
Inactivation by (Gatekeepers). inactive form. This prevents subsequent phosphorylation of
hypermethylation of its Rb protein and release of E2F factor.
promoter region. Loss of p16 results in constitutively expressed Cyclin D1-
Cdk 4 kinase and loss of control of passage from G1 to S
phase.
Gene deletion. Smad proteins These are components of TGF- β signalling pathway. Loss
(Gatekeepers). of these proteins inhibits TGF- β pathway and thus
contribute to cell proliferation.
The end product of TGF- β pathway are p15 protein and
PAI-1.
p15 protein is a G1 cyclin kinase inhibitor. It displaces p27
from cyclin D-Cdk 4 complex (this inactivates cyclin D-Cdk 4
complex) and this free p27 attaches itself to Cyclin E-Cdk 2
complex (This inhibits the Cyclin E-Cdk 2 complex). This
