Investigating Membrane-Bound transcription Regulators

Investigating Membrane-Bound transcription Regulators

Cells & Development, Microbiology & Infectious Disease

Bethan Martin, Bronte West, Freija Guntripp, Iqbal Dulloo

The membranes of the mammalian cell are host to many membrane-bound transcription regulators which need to be collocated to the nucleus to act on both inter and extracellular processes ​(1)​ . For our project we chose to focus on the membrane of the endoplasmic reticulum, which research has shown to be a region where proteins (or peptide fragments) are able to cycle between the ER and the nucleus in order to influence gene transcription.​(2)​ The pseudoproteases iRhom (of the rhomboid super family) ​(3)​ have been identified as such proteins with a distinct function related to their cleavage from the ER and subsequent nuclear transport. This cleavage is conducted via the Signal Peptidase Complex (SPC) which cleaves either side of the first transmembrane domain, resulting in an N terminal fragment. This fragment is then transported to the nucleus where it can affect gene expression. This process has been shown to be elevated in pathologies such as psoriasis and oesophageal cancer. ​(4)​ Our goal was to investigate if other proteins (TMEM214, TRPV4, TOR4A) with regions similar to iRhom cleavage sites undergo the same SPC cleavage mechanism. Evidence of cleavage would suggest the proteins could possess a similar transcription regulation function, potentially linking to other pathologies.