Emerging role of rhomboid family proteins in mammalian biology and disease

AbstractFrom proteases that cleave peptide bonds in the plane of the membrane, rhomboids have evolved into a heterogeneous superfamily with a wide range of different mechanistic properties. In mammals 14 family members have been annotated based on a shared conserved membrane-integral rhomboid core domain, including intramembrane serine proteases and diverse proteolytically inactive homologues. While the function of rhomboid proteases is the proteolytic release of membrane-tethered factors, rhomboid pseudoproteases including iRhoms and derlins interact with their clients without cleaving them. It has become evident that specific recognition of membrane protein substrates and clients by the rhomboid fold reflects a spectrum of cellular functions ranging from growth factor activation, trafficking control to membrane protein degradation. This review summarizes recent progress on rhomboid family proteins in the mammalian secretory pathway and raises the question whether they can be seen as new drug targets for inflammatory diseases and cancer. This article is part of a special issue entitled: Intramembrane Proteases

Knowledge, perceptions, and management of cancer-related fatigue: the patients' perspective

Purpose!#!This study aimed to assess cancer patients' knowledge and perceptions regarding fatigue and to provide up-to-date information on the current fatigue management from the patients' perspective.!##!Methods!#!The FiX study recruited 2508 cancer patients approximately 2 years after diagnosis via a cancer registry in Germany. Participants completed a questionnaire on their knowledge and perceptions of fatigue and the management received.!##!Results!#!More than half of respondents (58%), especially among the elderly patients, did not feel well informed about fatigue. Overall, 41% reported having never been asked about being exhausted by their treating physician. Even fewer patients stated that general practitioners or nurses have asked if they felt exhausted. Only 13% of patients who had experienced severe fatigue had received a fatigue assessment by means of a rating scale or questionnaire-although this is recommended by existing guidelines for fatigue screening. Health care professionals seemed less likely to address fatigue with elderly as well as female patients. The most commonly reported measure against fatigue was exercise or regular physical activity (68%). However, this was mostly done on patients' own initiative. Psychological support was rarely used (13%) and only in approximately half of the cases upon the advice of a physician. Yoga, another promising intervention against fatigue, was performed by only 9% of patients.!##!Conclusions!#!Our study indicates deficits in terms of knowledge, education, screening, counseling, and treatment for fatigue and highlights starting points for targeted improvements in fatigue management based on patients' needs