The rhomboids are a recently discovered family of intramembrane proteases that are conserved across evolution. Drosophila was the first organism in which they were characterized, where at least Rhomboids 1-3 activate EGF receptor signaling by releasing the active forms of EGF-like growth factors. Subsequent work has begun to shed light on the role of these proteases in bacteria and yeast, but n...

The rhomboid family of serine proteases occurs in all domains of life. Its members contain at least six hydrophobic membrane-spanning helices, with an active site serine located deep within the hydrophobic interior of the plasma membrane. The model member GlpG from Escherichia coli is heavily studied through engineered mutant forms, varied model substrates, and multiple X-ray crystal studies, y...

The rhomboid-like proteins constitute a large family of intramembrane serine proteases that are present in all branches of life. First studied in Drosophila, these enzymes catalyse the release of the active forms of proteins from the membrane and hence trigger signalling events. In protozoan parasites, a limited number of rhomboid-like proteases have been investigated and some of them are assoc...

Rhomboid serine proteases are present in many species with Background: sequenced genomes, and are often encoded in each species by more than one predicted gene. Based on protein sequence comparisons, rhomboids can be differentiated into groups secretases, presenilin-like associated rhomboid-like (PARL) proteases, iRhoms, and “inactive” rhomboid proteins. Although these rhomboid groups are disti...

Rhomboid proteases are evolutionary conserved intramembrane serine proteases. Because of their emerging role in many important biological pathways, rhomboids are potential drug targets. Unfortunately, few chemical tools are available for their study. Here, we describe a mass spectrometry-based assay to measure rhomboid substrate cleavage and inhibition. We have identified isocoumarin inhibitors...

Rhomboid-family intramembrane proteases regulate important biological processes and have been associated with malaria, cancer, and Parkinson's disease. However, due to the lack of potent, selective, and pharmacologically compliant inhibitors, the wide therapeutic potential of rhomboids is currently untapped. Here, we bridge this gap by discovering that peptidyl α-ketoamides substituted at the k...

Median rhomboid glossitis (MRG) is an uncommon benign abnormality of the tongue, most frequently affecting men. It is typically located around the midline of the dorsum of the tongue, anterior to the lingual "V", appearing as a reddish, rhomboid area, depapillated, flat maculate or mamillated and raised by 2 - 5 mm. This paper reports a case of rhomboid glossitis in a 61-year-old man who consul...

Rhomboids form a family of polytopic intramembrane serine proteases. In Toxoplasma gondii, an essential activity called microneme protein protease 1 (MPP1) cleaves secreted adhesive proteins within their transmembrane domains, at a site conserved in similar proteins of other Apicomplexa. Current evidence suggests that MPP1 is ubiquitous in the phylum and is encoded by a rhomboid gene. In this a...

Members of the widespread rhomboid family of intramembrane proteases cleave transmembrane domain (TMD) proteins to regulate processes as diverse as EGF receptor signaling, mitochondrial dynamics, and invasion by apicomplexan parasites. However, lack of information about their substrates means that the biological role of most rhomboids remains obscure. Knowledge of how rhomboids recognize their ...