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Review
. 2021 Oct 18;14(1):171.
doi: 10.1186/s13045-021-01184-1.

The roles of GTPase-activating proteins in regulated cell death and tumor immunity

Hua He #  1   2 , Jingjing Huang #  1   2 , Sufang Wu #  1   2 , Shiyao Jiang  1   2 , Lu Liang  1   2 , Yueying Liu  1   2 , Wenbing Liu  3 , Li Xie  3 , Yongguang Tao  4 , Yiqun Jiang  5   6 , Li Cong  7   8
Affiliations
Review

The roles of GTPase-activating proteins in regulated cell death and tumor immunity

Hua He et al. J Hematol Oncol. .

Abstract

GTPase-activating protein (GAP) is a negative regulator of GTPase protein that is thought to promote the conversion of the active GTPase-GTP form to the GTPase-GDP form. Based on its ability to regulate GTPase proteins and other domains, GAPs are directly or indirectly involved in various cell requirement processes. We reviewed the existing evidence of GAPs regulating regulated cell death (RCD), mainly apoptosis and autophagy, as well as some novel RCDs, with particular attention to their association in diseases, especially cancer. We also considered that GAPs could affect tumor immunity and attempted to link GAPs, RCD and tumor immunity. A deeper understanding of the GAPs for regulating these processes could lead to the discovery of new therapeutic targets to avoid pathologic cell loss or to mediate cancer cell death.

Keywords: GTPase-activating proteins; Regulated cell death; Tumor immunity.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
GAPs are multidomain proteins. GAPs have typical GAP active structural domains that interact with GTPase proteins, and other protein structural domains might also be present to play regulatory functions
Fig. 2
Fig. 2
Examples of the involvement of GAPs in tumor cell apoptosis. Some GAPs can promote apoptosis in tumor cells by regulating apoptosis-related proteins and pathways and thus become collaborators of antitumor drugs. Some GAPs also exert apoptosis-inhibiting effects and thus promote tumor progression
Fig. 3
Fig. 3
Signaling pathways of GAPs that affect nonapoptotic RCD. GAPs regulate vesicle transport and autophagosome maturation during autophagy and are involved in mTOR-related pathways. In addition, GAPs regulate ferroptosis, entosis, MC and other RCDs
Fig. 4
Fig. 4
Role of GAPs in immune activity. a GAPs are essential for maintaining normal immune cell activity. b NF1 deficiency participates in the formation of the relevant tumor immune microenvironment
See this image and copyright information in PMC

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