54864e74e213494817a370d0f5b9b04a pmc_33498168.pdf c52e54649585a70a42b6dbe21974e30b76fe9024 pmc_33498168.pdf 3e2b1bcef0d8326a8ee33915c0371208d68cbdffa2caccf44660fdf6bdb6a24a pmc_33498168.pdf Title: Molecular Mechanisms of DUBs Regulation in Signaling and Disease Subject: The large family of deubiquitinating enzymes (DUBs) are involved in the regulation of a plethora of processes carried out inside the cell by protein ubiquitination. Ubiquitination is a basic pathway responsible for the correct protein homeostasis in the cell, which could regulate the fate of proteins through the ubiquitin–proteasome system (UPS). In this review we will focus on recent advances on the molecular mechanisms and specificities found for some types of DUBs enzymes, highlighting illustrative examples in which the regulatory mechanism for DUBs has been understood in depth at the molecular level by structural biology. DUB proteases are responsible for cleavage and regulation of the multiple types of ubiquitin linkages that can be synthesized inside the cell, known as the ubiquitin-code, which are tightly connected to specific substrate functions. We will display some strategies carried out by members of different DUB families to provide specificity on the cleavage of particular ubiquitin linkages. Finally, we will also discuss recent progress made for the development of drug compounds targeting DUB proteases, which are usually correlated to the progress of many pathologies such as cancer and neurodegenerative diseases. Keywords: ubiquitin; deubiquitinating enzymes; UPS; proteasome; protein degradation; DUBs; USPs; ubiquitin-code; structural analysis Author: Ying Li and David Reverter Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Jan 25 04:16:53 2021 CET ModDate: Mon Jan 25 06:15:56 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 24 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 8219239 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UPFXVS+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 XXXOAS+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 VLZHOA+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 VJAUGW+VnURWPalladioL Type 1 Custom yes yes no 23 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 32 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C 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Title: DUBs Families and Linkage Specificity Destination: section.3 Children: Item: Title: Ovarian Tumor-Related Proteases, OTUs Destination: subsection.3.1 Item: Title: Ubiquitin-Specific Processing Enzymes, USPs/Ubiquitin-Specific Proteases, UBPs Destination: subsection.3.2 Item: Title: Jad1/Pad/MPN Domain-Containing Metalloenzymes, JAMM Family/MPN Destination: subsection.3.3 Item: Title: Machado Joseph Disease Proteases, MJDs/Josephin Destination: subsection.3.4 Item: Title: Ubiquitin C-Terminal Hydrolases, UCHs Destination: subsection.3.5 Item: Title: MIU-Containing Novel DUB Family, MINDY Destination: subsection.3.6 Item: Title: Zinc Finger with UFM1-Specific Peptidase Domain Protein/C6orf113/ZUP1 Destination: subsection.3.7 Item: Title: Regulatory Mechanisms of DUB Activity and Specificity Destination: section.4 Children: Item: Title: USP7, a Conformational Rearrangement of the Catalytic Triad Destination: subsection.4.1 Item: Title: Ubp8, Needs Partner Proteins for Activity Destination: subsection.4.2 Item: Title: USP25, an Auto-Inhibitory Homotetramer Destination: subsection.4.3 Item: Title: OTUB1, a Non-Canonical Inhibition of the E2-Conjugating Enzyme Destination: subsection.4.4 Item: Title: OTULIN, with a Little Help of Ubiquitin for Activation Destination: subsection.4.5 Item: Title: RPN11, Cleaves the Ubiquitin Chain in the 26S Proteasome Destination: subsection.4.6 Item: Title: USP12-UAF1-WDR20, Help of Partners for Activation Destination: subsection.4.7 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Molecular Mechanisms of DUBs Regulation in Signaling and Disease Author: Ying Li and David Reverter Subject: The large family of deubiquitinating enzymes (DUBs) are involved in the regulation of a plethora of processes carried out inside the cell by protein ubiquitination. Ubiquitination is a basic pathway responsible for the correct protein homeostasis in the cell, which could regulate the fate of proteins through the ubiquitin proteasome system (UPS). In this review we will focus on recent advances on the molecular mechanisms and specificities found for some types of DUBs enzymes, highlighting illustrative examples in which the regulatory mechanism for DUBs has been understood in depth at the molecular level by structural biology. DUB proteases are responsible for cleavage and regulation of the multiple types of ubiquitin linkages that can be synthesized inside the cell, known as the ubiquitin-code, which are tightly connected to specific substrate functions. We will display some strategies carried out by members of different DUB families to provide specificity on the cleavage of particular ubiquitin linkages. Finally, we will also discuss recent progress made for the development of drug compounds targeting DUB proteases, which are usually correlated to the progress of many pathologies such as cancer and neurodegenerative diseases. 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Link Rect: 407, 456, 444, 467 Annotation: Subtype: Link Rect: 516, 445, 553, 456 Annotation: Subtype: Link Rect: 520, 422, 557, 433 Checksum: bfaa1429 Type: CRC32 Checksum: 54864e74e213494817a370d0f5b9b04a Type: MD5 Checksum: c52e54649585a70a42b6dbe21974e30b76fe9024 Type: SHA-1 Checksum: 3e2b1bcef0d8326a8ee33915c0371208d68cbdffa2caccf44660fdf6bdb6a24a Type: SHA-256