Thinking inside the box: intracellular roles for complement system proteins come into focus
Over the last decade, perspectives on the complement system in the context of cancer have shifted, with complement proteins now implicated in many of the hallmarks of cancer. Systemically, the generation of complement anaphylatoxin C5a, the most potent inflammatory mediator of the cascade, occurs fo...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2023
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| _version_ | 1797109344928530432 |
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| author | O’Brien, RM Lynam-Lennon, N Olcina, MM |
| author_facet | O’Brien, RM Lynam-Lennon, N Olcina, MM |
| author_sort | O’Brien, RM |
| collection | OXFORD |
| description | Over the last decade, perspectives on the complement system in the context of cancer have shifted, with complement proteins now implicated in many of the hallmarks of cancer. Systemically, the generation of complement anaphylatoxin C5a, the most potent inflammatory mediator of the cascade, occurs following convertase-mediated cleavage of complement component C5. In a recent manuscript, Ding et al., propose that in colorectal cancer cells, C5 cleavage can occur intracellularly and in a convertase-independent manner, identifying cathepsin D as an enzyme capable of cleaving C5 into C5a [1]. Intracellular C5a is functional and promotes β-catenin stabilisation via the assembly of a KCTD5/cullin3/Roc-1 complex. Importantly, the blockade of C5aR1 prevents tumorigenesis. This study adds to a growing body of evidence indicating that complement proteins, previously thought to primarily have extracellular or membrane-bound functions, also have important intracellular roles. |
| first_indexed | 2024-03-07T07:40:35Z |
| format | Journal article |
| id | oxford-uuid:38482487-007f-42fe-846a-4828b1fa8bb6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:40:35Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:38482487-007f-42fe-846a-4828b1fa8bb62023-04-27T08:03:01ZThinking inside the box: intracellular roles for complement system proteins come into focusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:38482487-007f-42fe-846a-4828b1fa8bb6EnglishSymplectic ElementsSpringer Nature2023O’Brien, RMLynam-Lennon, NOlcina, MMOver the last decade, perspectives on the complement system in the context of cancer have shifted, with complement proteins now implicated in many of the hallmarks of cancer. Systemically, the generation of complement anaphylatoxin C5a, the most potent inflammatory mediator of the cascade, occurs following convertase-mediated cleavage of complement component C5. In a recent manuscript, Ding et al., propose that in colorectal cancer cells, C5 cleavage can occur intracellularly and in a convertase-independent manner, identifying cathepsin D as an enzyme capable of cleaving C5 into C5a [1]. Intracellular C5a is functional and promotes β-catenin stabilisation via the assembly of a KCTD5/cullin3/Roc-1 complex. Importantly, the blockade of C5aR1 prevents tumorigenesis. This study adds to a growing body of evidence indicating that complement proteins, previously thought to primarily have extracellular or membrane-bound functions, also have important intracellular roles. |
| spellingShingle | O’Brien, RM Lynam-Lennon, N Olcina, MM Thinking inside the box: intracellular roles for complement system proteins come into focus |
| title | Thinking inside the box: intracellular roles for complement system proteins come into focus |
| title_full | Thinking inside the box: intracellular roles for complement system proteins come into focus |
| title_fullStr | Thinking inside the box: intracellular roles for complement system proteins come into focus |
| title_full_unstemmed | Thinking inside the box: intracellular roles for complement system proteins come into focus |
| title_short | Thinking inside the box: intracellular roles for complement system proteins come into focus |
| title_sort | thinking inside the box intracellular roles for complement system proteins come into focus |
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