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SKP1-CUL1-F-box: Key Molecular Targets Affecting Disease Progression

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Journal FASEB J
Date 2025 Jan 15
PMID 39812503
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Abstract

The correct synthesis and degradation of proteins are vital for numerous biological processes in the human body, with protein degradation primarily facilitated by the ubiquitin-proteasome system. The SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase, a member of the Cullin-RING E3 ubiquitin ligase (CRL) family, plays a crucial role in mediating protein ubiquitination and subsequent 26S proteasome degradation during normal cellular metabolism. Notably, SCF is intricately linked to the pathogenesis of various diseases, including malignant tumors. This paper provides a comprehensive overview of the functional characteristics of SCF complexes, encompassing their assembly, disassembly, and regulatory factors. Furthermore, we discuss the diverse effects of SCF on crucial cellular processes such as cell cycle progression, DNA replication, oxidative stress response, cell proliferation, apoptosis, cell differentiation, maintenance of stem cell characteristics, tissue development, circadian rhythm regulation, and immune response modulation. Additionally, we summarize the associations between SCF and the onset, progression, and prognosis of malignant tumors. By synthesizing current knowledge, this review aims to offer a novel perspective for a holistic and systematic understanding of SCF complexes and their multifaceted functions in cellular physiology and disease pathogenesis.

Citing Articles

SKP1-CUL1-F-box: Key molecular targets affecting disease progression.

Zeng X, Cao J, Xu J, Zhou Z, Long C, Zhou Y FASEB J. 2025; 39(2):e70326.

PMID: 39812503 PMC: 11734646. DOI: 10.1096/fj.202402816RR.

References
1.
Jeong Y, Simoneschi D, Keegan S, Melville D, Adler N, Saraf A . The ULK1-FBXW5-SEC23B nexus controls autophagy. Elife. 2019; 7. PMC: 6351106. DOI: 10.7554/eLife.42253. View

2.
Gil-Bernabe A, Romero F, Limon-Mortes M, Tortolero M . Protein phosphatase 2A stabilizes human securin, whose phosphorylated forms are degraded via the SCF ubiquitin ligase. Mol Cell Biol. 2006; 26(11):4017-27. PMC: 1489102. DOI: 10.1128/MCB.01904-05. View

3.
Morel M, Shah K, Long W . The F-box protein FBXL16 up-regulates the stability of C-MYC oncoprotein by antagonizing the activity of the F-box protein FBW7. J Biol Chem. 2020; 295(23):7970-7980. PMC: 7278360. DOI: 10.1074/jbc.RA120.012658. View

4.
Cepeda D, Ng H, Sharifi H, Mahmoudi S, Cerrato V, Fredlund E . CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. EMBO Mol Med. 2013; 5(7):1067-86. PMC: 3721474. DOI: 10.1002/emmm.201202341. View

5.
Kanemori Y, Uto K, Sagata N . Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. Proc Natl Acad Sci U S A. 2005; 102(18):6279-84. PMC: 1083676. DOI: 10.1073/pnas.0501873102. View