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Review
. 2020 Jun 16;12(6):1595.
doi: 10.3390/cancers12061595.

The Impact of the Ubiquitin System in the Pathogenesis of Squamous Cell Carcinomas

Veronica Gatti  1 , Francesca Bernassola  2 , Claudio Talora  3 , Gerry Melino  2 , Angelo Peschiaroli  1
Affiliations
Review

The Impact of the Ubiquitin System in the Pathogenesis of Squamous Cell Carcinomas

Veronica Gatti et al. Cancers (Basel). .

Abstract

The ubiquitin system is a dynamic regulatory pathway controlling the activity, subcellular localization and stability of a myriad of cellular proteins, which in turn affects cellular homeostasis through the regulation of a variety of signaling cascades. Aberrant activity of key components of the ubiquitin system has been functionally linked with numerous human diseases including the initiation and progression of human tumors. In this review, we will contextualize the importance of the two main components of the ubiquitin system, the E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs), in the etiology of squamous cell carcinomas (SCCs). We will discuss the signaling pathways regulated by these enzymes, emphasizing the genetic and molecular determinants underlying their deregulation in SCCs.

Keywords: E3 ubiquitin ligase; deubiquitinating enzymes; oncogenes; squamous cell carcinoma; tumor suppressor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) The addition of ubiquitin to a target protein is a multistep, ATP-dependent process performed in three sequential enzymatic steps: activation of ubiquitin by an E1 ubiquitin activating enzyme, transfer of ubiquitin to one E2 ubiquitin conjugating enzyme and, lastly, the E3 ligase-mediated transfer of ubiquitin from E2 to the substrate protein. Ubiquitination can be reversed by deubiquitinating enzymes (DUBs), a family of isopeptidases that catalyze the removal of ubiquitin from target proteins. (B) Fate of ubiquitin-modified proteins. (C) Structural architecture and catalytic properties of HECT- and the RING finger-type E3s. HECT-type E3s form a thioester-linked intermediate with ubiquitin before catalyzing its transfer to the substrate. The RING-type E3s act as platforms for recruiting the E2 thioester-linked to ubiquitin and for juxtaposing the E2 and the substrate for the ubiquitin transfer. This family comprises of both monomeric and the multi-subunit E3s.
Figure 2
Figure 2
Mechanistic model describing the biological processes underlying the main molecular and genetic alterations of the ubiquitin system in SCCs. The indicated ubiquitin system-related factors are involved in cell cycle progression (A), anti-oxidant defense (B) and DNA damage checkpoint/inflammatory response (C). See text for details.
See this image and copyright information in PMC

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