progeria/protease

FACE 1 is the endoprotease responsible for cleavage of prelamin A to lamin A. Transfection of HeLa cells with siRNA for human FACE 1 results in a strong phenotype. Protein and mRNA levels for FACE 1 are knocked down and cell division stops abruptly. Two populations of cells are detected. The first

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder because of a LMNA gene mutation that produces a mutant lamin A protein (progerin). Progerin also has been correlated to physiological aging and related diseases. However, how progerin causes the progeria remains unknown. Here, we

Triosephosphate isomerase was found to have an increased thermolabile component in skin fibroblasts from patients with progeria and Werner's syndrome when compared with normal fibroblasts. Mixtures of cell extracts from progeria or Werner's syndrome with normal fibroblasts gave intermediate levels

Fibroblasts of a patient with the Hutchinson-Gilford progeria show a decreased proliferative activity in culture and run through no more than 19 subcultivations. Progeria cells rejoin gamma-induced single strand DNA breaks to the same extent and with the same rate as do normal cells. Spontaneous and

The glycosylation of proteins in fibroblasts from people with the premature ageing disease Hutchinson-Gilford Progeria Syndrome (progeria) was investigated. Protein was prepared from fibroblast cell lines established from skin biopsy taken from progeria patients and control donors. Glycoproteins

Hutchinson-Gilford progeria syndrome (HGPS) is a devastating premature aging disease resulting from a mutation in the LMNA gene, which encodes nuclear lamins A and C. Lamin A is synthesized as a precursor (prelamin A) with a C-terminal CaaX motif that undergoes farnesylation, endoproteolytic

BackgroundHutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare, fatal, segmental premature aging syndrome caused by the aberrant lamin A protein, progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease.MethodsWe performed a

Progeria syndromes have in common a premature aging phenotype and increased genome instability. The susceptibility to DNA damage arises from a compromised repair system, either in the repair proteins themselves or in the DNA damage response pathways. The most severe progerias stem from mutations

Prelamin A undergoes multistep processing to yield lamin A, a structural protein of the nuclear lamina. Prelamin A terminates with a CAAX motif, which triggers farnesylation of a C-terminal cysteine (the C of the CAAX motif), endoproteolytic release of the last three amino acids (the AAX), and

Genomic instability due to telomere dysfunction and defective repair of DNA double-strand breaks (DSBs) is an underlying cause of ageing-related diseases. 53BP1 is a key factor in DNA DSBs repair and its deficiency is associated with genomic instability and cancer progression. Here, we uncover a

In the presence of O2, Fe(III) or Cu(II), and an appropriate electron donor, a number of enzymic and nonenzymic oxygen free radical-generating systems are able to catalyze the oxidative modification of proteins. Whereas random, global modification of many different amino acid residues and extensive

Liver is a vital organ with many important functions, and the maintenance of normal hepatic function is necessary for health. As an essential mechanism for maintaining cellular homeostasis, autophagy plays an important role in ensuring normal organ function. Studies have indicated that the

Ste24, an integral membrane protein zinc metalloprotease, is found in every kingdom of eukaryotes. It was discovered approximately twenty years ago by yeast genetic screens identifying it as a factor responsible for processing the yeast mating a-factor pheromone. In animals, Ste24 processes prelamin

Ste24 enzymes, a family of eukaryotic integral membrane proteins, are zinc metalloproteases (ZMPs) originally characterized as "CAAX proteases" targeting prenylated substrates, including a-factor mating pheromone in yeast and prelamin A in humans. Recently, Ste24 was shown to also cleave

Two fibroblast cell lines (PG3KT and PG1NA) derived from Hutchinson-Gilford syndrome (progeria) cases were characterized, at various population doubling levels (PDL), with respect to the capacity of ultraviolet light (UV, mainly 254 nm wavelength)-induced unscheduled DNA synthesis (UDS) and