K6-linked ubiquitylation marks formaldehyde-induced RNA-protein crosslinks for resolution.

Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and they accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated.

Evolutionary expansion of polyaspartate motif in the activation peptide of mouse cationic trypsinogen limits autoactivation and protects against pancreatitis.

The activation peptide of mammalian trypsinogens typically contains a tetra-aspartate motif (positions P2-P5 in Schechter-Berger numbering) that inhibits autoactivation and facilitates activation by enteropeptidase. This evolutionary mechanism protects the pancreas from premature trypsinogen activation while allowing physiological activation in the gut lumen. Inborn mutations that disrupt the tetra-aspartate motif cause hereditary pancreatitis in humans.

Ethanol feeding accelerates pancreatitis progression in mutant mice.

Alcoholic pancreatitis is a multifactorial, progressive, inflammatory disorder of the pancreas. Alcohol initiates pancreatitis and promotes its progression in the context of genetic susceptibility and/or other environmental risk factors such as smoking. Genetic mutations can cause digestive enzyme misfolding, which induces endoplasmic reticulum (ER) stress and elicits pancreatitis.

A Novel Mutation in the Critical P-Box Residue of Steroidogenic Factor-1 Presenting with XY Sex Reversal and Transient Adrenal Failure.

Background: Although the importance of steroidogenic factor-1 (SF1, NR5A1) for adrenal development is supported by numerous in vitro and in vivo studies, cases of SF1 deficiency associated with adrenal failure are exceptionally rare. The first human NR5A1 mutation was a heterozygous de novo p.G35E variant identified in a patient with disorder of sex development (DSD) 46,XY and primary adrenal insufficiency.

Partial deficiency of 17α-hydroxylase/17,20-lyase caused by a novel missense mutation in the canonical cytochrome heme-interacting motif.

Background: Deficiency of 17α-hydroxylase/17,20-lyase is a rare cause of 46,XY disordered sex development.

Objective: We characterize in vitro and in vivo effects of two novel CYP17A1 gene mutations identified in a patient with a mild phenotype of CYP17A1 deficiency.

Subjects And Methods: A 46,XY patient presented with ambiguous genitalia.