Role of GSDMB in Pyroptosis and Cancer

Figures & data

Figure 1 GSDMB is different from other gasdermins in its structure and domain architecture. The protein of GSDMA (A), GSDMB (B), GSDMC (C), GSDMD (D) and GSDME (E) is shown as cartoon. Blue cartoon represents the helices of protein. Red cartoon represents the sheets of protein. Yellow cartoon represents the coils of protein.

Figure 2 Cleavage of GSDMB protein by caspase-1 induces pyroptosis. Caspase-1 promotes the cleavage of GSDMB and the releasing of the N-terminal effector domain and the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms pores, which leads to pyroptosis.

Figure 3 GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity. The binding of GSDMB with the CARD domain of caspase-4 result in the oligomerization of the caspase-4 proteins, and caspase-4 promotes the cleavage of GSDMD and the releasing of the N-terminal effector domain and the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms pores, which leads to pyroptosis.

Figure 4 GSDMB could be cleaved by caspase-3/-6/-7. Caspase-3/-6/-7 promotes the cleavage of GSDMB and the releasing of the N-terminal effector domain and the C-terminal inhibitory domain.

Table 1 Differences in the Experiments About the Mechanism of GSDMB in Pyroptosis

Cell Signaling	Cell Lines	Activated Conditions	Methods	Cleavage Sites	References
Cleavage of GSDMB protein by caspase-1	Human ciliated airway epithelial cells	Pro-inflammatory stimuli such as viruses and allergens	Cytotoxicity assay, microscopic examination	D236A mutant	[^Citation39,Citation46,Citation47]
GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity	Human embryonic kidney (HEK)	FuGENE HD	Measurement of caspase-4 activity, cytotoxicity assay, co-immunoprecipitation studies	–	[^Citation48,Citation49]
Cleavage of GSDMB protein by caspase-3/-6/-7	The human GSDMB gene was amplified from a cDNA clone and was ligated for expression in E. coli.	–	In vitro caspase cleavage assay, Western analyses	88DNVD91 site	[^Citation30,Citation35,Citation39]

Table 2 GSDMB in Different Cancers

Cancer Type	Expression in Cancer	GSDMB in Cancer Cell Invasion, Progression, and Metastasis	The Role of GSDMB in Marker of Cancer	The Role of GSDMB in Prognosis	The Role of GSDMB in Therapy	References
Breast cancer	Upregulation	Correlation	A marker in cancer screening	A critical determinant	Antibody targeting GSDMB Cytoplasmic overexpression of GSDMB	[^Citation33,Citation50^–^Citation52]
Gastric cancer	Upregulation	Correlation	A marker for the evaluation of cancer development and progression	–	The GSDMB-driven expression vector	[^Citation34,Citation54^–^Citation56]
Cervical cancer	Upregulation	Correlation	An evaluation indicator in onset risk during the normal to cancer transition process	–	–	[^Citation59,Citation60]

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