Comprehensive Report: Proteolysis and Notch Signaling in Cell Biology

This report examines the crucial role of proteolysis in the Notch/Delta pathway within cell biology. It details how proteolysis, initiated by Lingad binding, leads to the activation of the Notch receptor through a two-step process involving ectodomain and intramembranous cleavage. This process releases the Notch intracellular domain, which translocates to the nucleus to regulate transcription. The report highlights the significance of Notch signaling in vertebrate physiology, including vascular development, and emphasizes the importance of regulated signaling pathways. It underscores the physiological and pathological implications of proteolysis in this context, providing a comprehensive understanding of its importance in cellular processes and signaling mechanisms. References from various studies support the analysis of the role of proteolysis in the Notch/Delta pathway and its impact on cell signaling.

Running head: CELL BIOLOGY 1
Proteolysis
Name
Institution

CELL BIOLOGY 2
Proteolysis and Notch Signaling
Proteolysis can be described as a regulatory event that acts to control the extracellular and
intracellular signaling by irreversibly changing the structure of a protein thereby altering its
functionality (Wysocka & Lesner, 2013). Proteolysis is very important in Notch/Delta pathways
because it releases an intracellular fragment that is directly involved in the transcriptional
regulation of nuclear target genes to activate the Notch receptor. Proteolysis leads to Notch
activation with the help of Lingad binding. This Notch activation undergoes two proteolytic
cleavages known as ectodomain cleavage and intramembranous cleavage (Van Tetering &
Vooijs, 2011). This can be described as a two-step activation and it helps in both physiological
and pathological signaling of the Notch/Delta pathway. The two-step activation which is also
called the regulated intramembrane proteolysis releases the Notch intracellular domain that binds
to the transcription factor after trans-locating to the nucleus thus activating the target genes (Van
Tetering & Vooijs, 2011).
It is important to note that proteolysis results from Lingad binding thus initiating the production
of Notch intracellular domain that links with CSL in the nucleus to trigger transcription. The
Notch intracellular domain helps in converting the Notch receptor into a downstream signal
transducer. The role of Notch signaling plays is essential in physiology and vascular
developments in vertebrates (Shehzad & Lee, 2013). The Notch signaling pathway is very
conserved and regulated to ensure that the polarity, duration, and intensity of the signaling are
fine-tuned. This role of proteolysis in the Notch/Delta pathway is thus important because it
supports several physiological and pathological mechanisms in vertebrates. The diagram below
is a depiction of proteolysis and its importance in the Notch/Delta pathway.

CELL BIOLOGY 3
(Kannan et al., 2018)

CELL BIOLOGY 4
References
Kannan, R., Cox, E., Wang, L., Kuzina, I., Gu, Q., & Giniger, E. (2018). Tyrosine
phosphorylation and proteolytic cleavage of Notch are required for non-canonical
Notch/Abl signaling in Drosophila axon guidance. Development, 145(2), dev151548.
Shehzad, A., & Lee, Y. S. (2013). Molecular mechanisms of curcumin action: signal
transduction. Biofactors, 39(1), 27-36.
Van Tetering, G., & Vooijs, M. (2011). Proteolytic cleavage of Notch:“HIT and RUN”. Current
molecular medicine, 11(4), 255-269.
Wysocka, M., & Lesner, A. (2013). Future of protease activity assays. Current pharmaceutical
design, 19(6), 1062-1067.