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Review
. 2021 Jun 19;21(1):315.
doi: 10.1186/s12935-021-02012-9.

RSF1 in cancer: interactions and functions

Guiyang Cai  1 , Qing Yang  2 , Wei Sun  3
Affiliations
Review

RSF1 in cancer: interactions and functions

Guiyang Cai et al. Cancer Cell Int. .

Abstract

RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.

Keywords: CENP-A; H2Aub; NF-κB; PLK1; RSF1; SNF2H.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schematic representation of RSF1 functional domain
Fig. 2
Fig. 2
The overexpression status of RSF1 in different tumors compared with the adjacent normal tissues or normal tissues based on TCGA and GTEX databases. TPM represents transcription per million, *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 3
Fig. 3
The overexpression status of SNF2H in different tumors compared with the adjacent normal tissues or normal tissues based on TCGA and GTEX databases. TPM represents transcription per million, *P < 0.05, **P < 0.01, ***P < 0.001
Fig. 4
Fig. 4
RSF1 interactions and functions involved in cancer. a RSF1 interacts with ATM and is phosphorylated by ATM, then to interact with CENP-S/MHF1 to recruit FANCI/FANCD2 at DSBs to promote DNA HR repair, RSF1 interacts with ATM and is phosphorylated by ATM to decrease the upregulated protein level of RSF1 upon DNA damage. b RSF1 interacts with HBX and BubR1 to recruit HBX at kinetochore to decrease BubR1-Cdc20 interaction to inhibit metaphase-to-anaphase mitotic checkpoint. c RSF1 interacts with H2Aub to suppress oncogene transcription. d over-expressed RSF1 recruits CBP to interact with NF-κB, and then activate NF-κB induced transcription to increase chemoresistance. e RSF1 interacts with and recruits PLK1 to kinetochore to phosphorylate BubR1 to maintain accurate chromosome arrangement. f RSF1 interacts with cyclin E1 to increase CDK2 activity to inhibit G1/S checkpoint. g RSF1 recruits CENP-A to centromere to maintain accurate chromosome segregation. h RSF1 interacts with and recruits HDAC1 to centromere to protect centromeric cohesion. i RSF1 interacts with SNF2H to make SNF2H enter nucleus to stabilize SNF2H, RSF1 interacts with SNF2H to maintain the protein homeostasis of RSF1 in the absence of DNA damage, over-expressed RSF1 interacts with SNF2H to promote tumor growth
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