Apoptosis or programmed cell death is regulated by two methods, intrinsic or extrinsic. The extrinsic method is based upon receptor mediated cell death. The details of this method are given below: Initiation: Under condition of stress/signal, the cells secrete death-initiation moleucules such as cytokines and signal transducers. TNF alpha is such a signal transducer molecule which also exerts inflammatory response. The signal molecule such as TNF alpha binds to its surface receptor present on the cell surface. The surface receptor is a transmembrane protein which comprises of intracellular executioner domains. Upon binding of TNF alpha activates this signalling cascade and the sequence of events is executed. Execution: Upon binding of TNF alpha to extracellular domain, the intracellular domain undergoes confirmational changes along with activation by phosphorylation of specific amino acid in the polypeptide sequence. This activation of intracellular domain releases secondary messanger molecules, mostly a small biomolecule which further transmits the signal. This secondary messanger binds to a receptor sequence in the nuclear membrane or activates a secondary signal regulator domain in the cytoplasm. If this signalling molecule is transferred to the cytoplasmic receptor, a sequence of biochemical reactions will activate caspase 2, 8 and 10 which will interact with the degrading organelles of the cells such as lysosomes and bring about intracellular self-digestion of the cell. Otherwise, the secondary messanger might be transferred to the nucleus where it can initiate a genetic executionary even of inflammatory response and bring irreversible physical damage to the DNA such as single strand 3\' OH- strand breakage. This will cause ultimately damage to the genetic material and further aggravate the cell death signalling by multiple pathways such as excessive free radical generation. Regulation: At many steps, this extracellular apoptotic pathway is regulated in the cell. Firstly, the transduction of signalling molecule is always tightly regulated by specificity between the signal and its surface receptor. Secondly, the activation of intracellular domain such as TNF alpha transmembrane death receptor domain or TRADD is an ATP dependent activation unit hence is controlled tightly by the cell. Third, the activation of death signal in the DNA is not very smooth process but it requires transit of the apoptotic signal through various rectification processes in the nucleus itself. Finally, the cell always tries to cope up with the stress/stimulus by modulating its physiological processes even in the presence of a death signal by undergoind metabolic, redox and bio-energetic changes. Thus, the process of receptor mediated apoptosis is tightly regulated in the cells at every step of initiation, execution and regulation in order to ensure homeostasis. Solution Apoptosis or programmed cell death is regulated by two methods, intrinsic or extrinsic. The extr.

1. Apoptosis or programmed cell death is regulated by two methods, intrinsic or extrinsic. The
extrinsic method is based upon receptor mediated cell death. The details of this method are given
below:
Initiation: Under condition of stress/signal, the cells secrete death-initiation moleucules such as
cytokines and signal transducers. TNF alpha is such a signal transducer molecule which also
exerts inflammatory response. The signal molecule such as TNF alpha binds to its surface
receptor present on the cell surface. The surface receptor is a transmembrane protein which
comprises of intracellular executioner domains. Upon binding of TNF alpha activates this
signalling cascade and the sequence of events is executed.
Execution: Upon binding of TNF alpha to extracellular domain, the intracellular domain
undergoes confirmational changes along with activation by phosphorylation of specific amino
acid in the polypeptide sequence. This activation of intracellular domain releases secondary
messanger molecules, mostly a small biomolecule which further transmits the signal. This
secondary messanger binds to a receptor sequence in the nuclear membrane or activates a
secondary signal regulator domain in the cytoplasm. If this signalling molecule is transferred to
the cytoplasmic receptor, a sequence of biochemical reactions will activate caspase 2, 8 and 10
which will interact with the degrading organelles of the cells such as lysosomes and bring about
intracellular self-digestion of the cell. Otherwise, the secondary messanger might be transferred
to the nucleus where it can initiate a genetic executionary even of inflammatory response and
bring irreversible physical damage to the DNA such as single strand 3' OH- strand breakage.
This will cause ultimately damage to the genetic material and further aggravate the cell death
signalling by multiple pathways such as excessive free radical generation.
Regulation: At many steps, this extracellular apoptotic pathway is regulated in the cell. Firstly,
the transduction of signalling molecule is always tightly regulated by specificity between the
signal and its surface receptor. Secondly, the activation of intracellular domain such as TNF
alpha transmembrane death receptor domain or TRADD is an ATP dependent activation unit
hence is controlled tightly by the cell. Third, the activation of death signal in the DNA is not very
smooth process but it requires transit of the apoptotic signal through various rectification
processes in the nucleus itself. Finally, the cell always tries to cope up with the stress/stimulus by
modulating its physiological processes even in the presence of a death signal by undergoind
metabolic, redox and bio-energetic changes.
Thus, the process of receptor mediated apoptosis is tightly regulated in the cells at every step of
initiation, execution and regulation in order to ensure homeostasis.
Solution

2. Apoptosis or programmed cell death is regulated by two methods, intrinsic or extrinsic. The
extrinsic method is based upon receptor mediated cell death. The details of this method are given
below:
Initiation: Under condition of stress/signal, the cells secrete death-initiation moleucules such as
cytokines and signal transducers. TNF alpha is such a signal transducer molecule which also
exerts inflammatory response. The signal molecule such as TNF alpha binds to its surface
receptor present on the cell surface. The surface receptor is a transmembrane protein which
comprises of intracellular executioner domains. Upon binding of TNF alpha activates this
signalling cascade and the sequence of events is executed.
Execution: Upon binding of TNF alpha to extracellular domain, the intracellular domain
undergoes confirmational changes along with activation by phosphorylation of specific amino
acid in the polypeptide sequence. This activation of intracellular domain releases secondary
messanger molecules, mostly a small biomolecule which further transmits the signal. This
secondary messanger binds to a receptor sequence in the nuclear membrane or activates a
secondary signal regulator domain in the cytoplasm. If this signalling molecule is transferred to
the cytoplasmic receptor, a sequence of biochemical reactions will activate caspase 2, 8 and 10
which will interact with the degrading organelles of the cells such as lysosomes and bring about
intracellular self-digestion of the cell. Otherwise, the secondary messanger might be transferred
to the nucleus where it can initiate a genetic executionary even of inflammatory response and
bring irreversible physical damage to the DNA such as single strand 3' OH- strand breakage.
This will cause ultimately damage to the genetic material and further aggravate the cell death
signalling by multiple pathways such as excessive free radical generation.
Regulation: At many steps, this extracellular apoptotic pathway is regulated in the cell. Firstly,
the transduction of signalling molecule is always tightly regulated by specificity between the
signal and its surface receptor. Secondly, the activation of intracellular domain such as TNF
alpha transmembrane death receptor domain or TRADD is an ATP dependent activation unit
hence is controlled tightly by the cell. Third, the activation of death signal in the DNA is not very
smooth process but it requires transit of the apoptotic signal through various rectification
processes in the nucleus itself. Finally, the cell always tries to cope up with the stress/stimulus by
modulating its physiological processes even in the presence of a death signal by undergoind
metabolic, redox and bio-energetic changes.
Thus, the process of receptor mediated apoptosis is tightly regulated in the cells at every step of
initiation, execution and regulation in order to ensure homeostasis.