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Review
. 2024 Nov 11;24(1):374.
doi: 10.1186/s12935-024-03563-3.

E3 ubiquitin ligase HECW2: a promising target for tumour therapy

Hui Shen #  1 , Qianrui Kou  1 , Linxin Shao  1 , Jing Zhang  2   3 , Fang Li #  4
Affiliations
Review

E3 ubiquitin ligase HECW2: a promising target for tumour therapy

Hui Shen et al. Cancer Cell Int. .

Abstract

Ubiquitination is a prevalent post-translational modification that plays a crucial role in a wide range of pathophysiological processes, including cell proliferation, apoptosis, autophagy, immune response, and DNA damage repair. Among the enzymes involved in ubiquitination, E3 ubiquitin ligases are particularly significant, serving as key regulators of numerous diseases, including tumours. This review focuses on HECW2 (HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2, also known as NEDL2), providing a comprehensive overview of its interactors and its pathological roles in tumorous cancer and other diseases. The insights gained from this review may contribute to the development of novel treatment strategies for various diseases, particularly tumours.

Keywords: E3 ubiquitin ligase HECW2; Immune infiltration; Interacting proteins; Pathological roles; Prognosis; Tumours.

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Conflict of interest statement

Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Conflict of interest The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
HECTtype E3 ligases. HECT type E3 ligases can be classified into three subfamilies: the NEDD4 subfamily with WW domains, the HERC subfamily with RLD-like domains and other HECT-type E3 ubiquitin ligases lacking WW and RLD domains
Fig. 2
Fig. 2
Illustration of the subcellular localization and protein structure of HECW2. (A) The genomic position of the HECW2 gene on the chromosome from the GeneCards database. (B) The subcellular localization of the HECW2 protein from the GeneCards database. (C) The primary structure of HECW2 from the PhosphoSitePlus® database. (D) The advanced structure of HECW2 from GeneCards database, the PDB ID for HECW2 is 2LFE
Fig. 3
Fig. 3
The expression levels of HECW2 mRNA and protein. (A-C) The mRNA relative expression levels of HECW2 in normal tissues from UCSC Xena, RNA-Seq Atlas and NCBI databases, respectively. (D-F) The relative mRNA expression levels of HECW2 in tumour tissues from UALCAN, GEPIA, and Sangerbox databases, respectively. (G) The protein expression levels of HECW2 in KIRC, COAD, and LUAD from HPA database. (H) The protein expression levels of HECW2 in KIRC, COAD, and STAD cell lines evaluated by western blotting
Fig. 4
Fig. 4
The correlation between HECW2 expression levels and OS(A), DSS (B), PFI(C) and DFI(D) in pan-cancer
Fig. 5
Fig. 5
The association between HECW2 expression levels and immune cell abundance(A), chemokines(B) and chemokine receptors(C) in pan-cancer
Fig. 6
Fig. 6
The correlation between HECW2 expression levels and immunosuppressants (A), immunostimulators (B) and MHC molecules (C) in pan-cancer
Fig. 7
Fig. 7
The interacting proteins, candidate substrates and E3 ligases of HECW2. (A-B) The interacting proteins identified from STRING database and IntAct database. (C-D) The candidate substrates and E3 ligases of HECW2 from Ubibrowser database
Fig. 8
Fig. 8
The pathological implications of HECW2 in tumours and nervous system diseases
See this image and copyright information in PMC

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