CASP3

CASP3 Full Name

caspase 3, apoptosis-related cysteine peptidase

CASP3 Introduction

Caspase-3 is a widely expressed member of the conserved protein family and is generally recognized for its activating proteolytic role in apoptosis in response to specific extrinsic or intrinsic inducers of this cell death pattern. However, there is increasing evidence that caspase-3 also plays a key role in regulating the growth and homeostasis maintenance of normal and malignant cells and tissues in multicellular organisms. Given that yeast has an ancestral caspase like gene, this suggests that caspase-3 protein may have acquired different functions in late evolution to better meet the needs of more complex multicellular organisms, but it may not necessarily lose all functions of its ancestral yeast precursor.

Figure 1. Strcuture of caspase 3.(Source: Eskandari, E, 2022)

Structure and regulation of Caspase-3
Caspase-3, a member of the caspase family, is known for its ability to mediate the cleavage of specific target proteins. Caspases are initially produced as inactive zymogens (known as pre caspases), and then they are activated by various specific internal and / or external signals. The molecular structure of procaspase-3 includes an N-terminal prodomain and two subunits, one large and one small (called P20 and P10, respectively). In mammals, the 18 caspases identified have been subdivided into two subfamilies according to their structure, function, and substrate specificity, commonly known as inflammatory and apoptotic caspases. Caspases-1, -4, -5, -11, -12, and -13 belong to the subfamily of inflammatory caspases, which have a preference for the substrate sequence Trp Glu his ASP. The apoptotic subfamily of caspases includes two subgroups called promoter / apical and effector / executor caspases. Apoptotic stimuli trigger the activation of promoter caspases (caspase-2, -8, -9, and -10), which then cleave and thereby activate effector members (Caspase-3, -6, and -7).

The Role of Caspase-3 in the Induction of Apoptosis
Cell death can be achieved by a variety of different mechanisms. During the development of cell renewal tissues and the whole life process, many cells are continuously eliminated through the mechanism of inducing apoptosis. Apoptosis can be triggered by interactions with extracellular factors and intrinsic (intracellular) events. Extrinsic factors can be steroid hormones as well as various ligands of the tumor necrosis factor (TNF) receptor superfamily (e.g., FasL, trail, tnf- α). Extracellular mediated binding of ligands to one of these death receptors leads to the binding of caspase-8 to Fas associated through the death domain (FADD) adaptor protein, thereby forming the death inducing signaling complex (disc). Recruitment of caspase-8 to the disc facilitates its oligomerization and activation by self cleavage. Cleaved caspase-8 then induces the activation of downstream effector caspases, whose activity subsequently leads to the final stage of apoptotic cell death

Figure 2.Mechanism of Caspase-3 regulating cell cycle progression.

Alternate Names for CASP3

CASP3; caspase 3, apoptosis-related cysteine peptidase; CPP32; SCA-1; CPP32B; caspase-3; CASP-3; CPP-32; apopain; procaspase3; protein Yama; PARP cleavage protease; cysteine protease CPP32; SREBP cleavage activity 1; caspase 3, apoptosis-related cysteine protease;

• 1.Eskandari, E., & Eaves, C. J. Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. Journal of Cell Biology, 2022, 221(6), e202201159.