Prelamin A Farnesylation and Progeroid Syndromes
نویسندگان
چکیده
منابع مشابه
DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A.
The genetic diseases Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD) arise from accumulation of farnesylated prelamin A because of defects in the lamin A maturation pathway. Both of these diseases exhibit symptoms that can be viewed as accelerated aging. The mechanism by which accumulation of farnesylated prelamin A leads to these accelerated aging phenotypes is not ...
متن کاملBlocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.
Defects in the biogenesis of lamin A from its farnesylated precursor, prelamin A, lead to the accumulation of prelamin A at the nuclear envelope, cause misshapen nuclei, and result in progeroid syndromes. A deficiency in ZMPSTE24, a protease involved in prelamin A processing, leads to prelamin A accumulation, an absence of mature lamin A, misshapen nuclei, and a lethal perinatal progeroid syndr...
متن کاملCompound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype.
H utchinson–Gilford progeria syndrome (HGPS; OMIM 176670) is an extremely rare but devastating disorder that mimics premature aging. Affected children appear normal at birth but typically develop failure to thrive in the first two years. Other features include alopecia, micrognathia, loss of subcutaneous fat with prominent veins, abnormal dentition, sclerodermatous skin changes, and osteolysis ...
متن کاملA mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder.
In 1994 in the Journal of Cell Science, Hennekes and Nigg reported that changing valine to arginine at the endoproteolytic cleavage site in chicken prelamin A abolishes its conversion to lamin A. The consequences of this mutation in an organism have remained unknown. We now report that the corresponding mutation in a human subject leads to accumulation of prelamin A and causes a progeroid disor...
متن کاملFarnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors.
Three mammalian nuclear lamin proteins, lamin B(1), lamin B(2) and the lamin A precursor, prelamin A, undergo canonical farnesylation and processing at CAAX motifs. In the case of prelamin A, there is an additional farnesylation-dependent endoproteolysis, which is defective in two congenital diseases: Hutchinson-Gilford progeria (HGPS) and restrictive dermopathy (RD). These two diseases arise r...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2006
ISSN: 0021-9258
DOI: 10.1074/jbc.r600033200