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Abstract Mechanistic target of rapamycin complex 1 (mTORC1) is a conserved serine/threonine kinase that integrates various environmental signals to regulate cell growth and metabolism. mTORC1 activation requires tethering to lysosomes by the Ragulator‐Rag complex. However, the dynamic regulation of the interaction between Ragulator and Rag guanosine triphosphatase (GTPase) remains unclear. In this study, that LAMTOR1, an essential component of Ragulator, is dynamically ubiquitinated depending on amino acid abundance is reported. It is found that the E3 ligase TRAF4 directly interacts with LAMTOR1 and catalyzes the K63‐linked polyubiquitination of LAMTOR1 at K151. Ubiquitination of LAMTOR1 by TRAF4 promoted its binding to Rag GTPases and enhanced mTORC1 activation, K151R knock‐in or TRAF4 knock‐out blocks amino acid‐induced mTORC1 activation and accelerates the development of inflammation‐induced colon cancer. This study revealed that TRAF4‐mediated LAMTOR1 ubiquitination is a regulatory mechanism for mTORC1 activation and provides a therapeutic target for diseases involving mTORC1 dysregulation.

Frank’s sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient’s chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.

Abstract The case report aims to reveal de Winter's electrocardiogram (ECG) pattern as an equivalent to anterior ST‐segment elevation myocardial infarction (STEMI). We report a case of a 49‐year‐old man with a history of smoking who presented to the emergency department with a 1 day history of chest pain that was exacerbated 5 h prior to presentation. Detailed clinical investigations and coronary angiographic characteristics were recorded. The first ECG of the patient was consistent with de Winter syndrome. Acute coronary artery angiography showed that the proximal left anterior descending coronary artery was completely occluded after the first diagonal branch artery was given off. A percutaneous coronary intervention was immediately performed. Our case indicates that early identification and diagnosis of such ECGs and timely reperfusion therapy of de Winter syndrome as a STEMI equivalent are required to improve the prognosis of such patients.