Oxford University scientists researching PAD4, a protein that plays a role in the development of inflammatory diseases like arthritis and which is regularly found in cancers have uncovered the protein's role in cancer development. Their results are published online by the journalScience Advances.
Peptidyl arginine deiminase 4 (PAD4) is an enzyme that plays a role in genetic expression - turning our genetic code into functional products in the body.
The team set out to understand the mechanisms by which PAD4 was involved. They found that PAD4 is attracted by another protein called E2F-1, which regulates various activities within cells. E2F-1 plays a role in cancer spread - proliferation as it's called - but the scientists found that PAD4, working with another protein called BRD4, could switch E2F-1 from promoting proliferation to promoting inflammation.
PAD4 changes a part of the E2F-1 protein, an amino acid called arginine, into another amino acid called citrulline. The resulting citrullinated E2F-1 attracts BRD4, which is able to bind to parts of the E2F known as acetylation marks. The resulting protein complex drives the expression of inflammatory genes, so increasing the amount of inflammation.
Having established that both PAD4 and BRD4 played a role, the scientists then looked at what happened when the two proteins were suppressed. Using mice with arthritis, they administered two treatments that inhibited PAD4 and BRD4.
Professor said: 'Suppressing either of the proteins reduced the symptoms of arthritis but suppressing both saw a marked reduction. Tests also showed that inflammatory products in the body of the mice were reduced. That confirmed the role of both PAD4 and BRD4 is switching E2F-1 to an inflammation role.
'Inflammation plays a key role in a number of cancers. For example, bowel cancer has an early inflammatory stage. By understanding the biological mechanisms that underlie these cancers, we are better placed to find effective treatments.'
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Enzyme location controls enzyme activity
Read more
Channel selectivity to ions explained!
Read more
New interaction mechanism of proteins discovered
Read more
DNA scissors can cut RNA, too
Read more
Mitochondria-to-nucleus messenger protein
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar