Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases.

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD.

Structural Basis for the Enzymatic Activity of the HACE1 HECT-Type E3 Ligase Through N-Terminal Helix Dimerization.

HACE1 is an ankyrin repeat (AKR) containing HECT-type E3 ubiquitin ligase that interacts with and ubiquitinates multiple substrates. While HACE1 is a well-known tumor suppressor, its structure and mode of ubiquitination are not understood. The authors present the cryo-EM structures of human HACE1 along with in vitro functional studies that provide insights into how the enzymatic activity of HACE1 is regulated.

HOX epimutations driven by maternal SMCHD1/LRIF1 haploinsufficiency trigger homeotic transformations in genetically wildtype offspring.

The body plan of animals is laid out by an evolutionary-conserved HOX code which is colinearly transcribed after zygotic genome activation (ZGA). Here we report that SMCHD1, a chromatin-modifying enzyme needed for X-inactivation in mammals, is maternally required for timely HOX expression. Using zebrafish and mouse Smchd1 knockout animals, we demonstrate that Smchd1 haplo-insufficiency brings about precocious and ectopic HOX transcription during oogenesis and embryogenesis.

Exploring the "Other" subfamily of HECT E3-ligases for therapeutic intervention.

The HECT E3 ligase family regulates key cellular signaling pathways, with its 28 members divided into three subfamilies: NEDD4 subfamily (9 members), HERC subfamily (6 members) and "Other" subfamily (13 members). Here, we focus on the less-explored "Other" subfamily and discuss the recent findings pertaining to their biological roles. The N-terminal regions preceding the conserved HECT domains are significantly diverse in length and sequence composition, and are mostly unstructured, except for short regions that incorporate known substrate-binding domains.

Structural insights into a HECT-type E3 ligase AREL1 and its ubiquitination activities .

The HECT E3 ligase family comprises three subfamilies: NEDD4 E3 ubiquitin protein ligase (NEDD4), HECT and RLD domain-containing E3 ubiquitin protein ligase (HERC), and "other." Most previous studies have focused on the NEDD4 subfamily. Apoptosis-resistant E3 ligase 1 (AREL1) belongs to "other" subfamily HECT that inhibits apoptosis by ubiquitinating and degrading proapoptotic proteins.