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- La progerina (UniProt# P02545-6) és una versió truncada de la proteïna lamina A implicada en la patologia de la síndrome de progèria de Hutchinson-Gilford . La progerina es pot generar per un polimorfisme esporàdic de nucleòtids d'un sol punt c.1824 C>T (GGC -> GGT, p. Gly608Gly) en el gen que codifica per a la lamina A madura. Aquesta mutació activa un lloc d'empalmament críptic que indueix una mutació en la lamina A prematura amb la supressió d'un grup de 50 aminoàcids prop de l' extrem C-terminal . L'endopeptidasa ZMPSTE24 no pot escindir entre la seqüència d'aminoàcids RSY - LLG que falta (com es veu a la figura) durant la maduració de la lamina A, a causa de la supressió dels 50 aminoàcids que incloïen aquesta seqüència. Això deixa la lamina A prematura intacta unida al grup carboxil farnesil metilat creant la proteïna defectuosa Progerina, en lloc de la proteïna madurada desitjada Lamin A. Aproximadament el 90% de tots els casos de síndrome de progèria de Hutchinson-Gilford són heterozigots per a aquest polimorfisme deleteri d'un sol nucleòtid dins de l'exó 11 del gen LMNA causant les modificacions post-traduccions per produir progerina. (ca)
- Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> GGT, p.Gly608Gly) in the gene that codes for matured Lamin A. This mutation activates a cryptic splice site that induces a mutation in premature Lamin A with the deletion of a 50 amino acids group near the C-terminus. The endopeptidase ZMPSTE24 cannot cleave between the missing RSY - LLG amino acid sequence (as seen in the figure) during the maturation of Lamin A, due to the deletion of the 50 amino acids which included that sequence. This leaves the intact premature Lamin A bonded to the methylated carboxyl farnesyl group creating the defective protein Progerin, rather than the desired protein matured Lamin A. Approximately 90% of all Hutchinson–Gilford progeria syndrome cases are heterozygous for this deleterious single nucleotide polymorphism within exon 11 of the LMNA gene causing the post-translational modifications to produce Progerin. Lamin A constitutes a major structural component of the lamina, a scaffold of proteins found inside the nuclear membrane of a cell; progerin does not properly integrate into the lamina, which disrupts the scaffold structure and leads to significant disfigurement of the nucleus, characterized by a globular shape. Progerin activates genes that regulate stem cell differentiation via the Notch signaling pathway. Progerin increases the frequency of unrepaired double-strand breaks in DNA following exposure to ionizing radiation. Also, overexpression of progerin is correlated with an increase in non-homologous end joining relative to homologous recombination among those DNA double-strand breaks that are repaired. Furthermore, the fraction of homologous recombination events occurring by gene conversion is increased. These findings suggest that the normal untruncated nuclear lamina has an important role in the proper repair of DNA double-strand breaks. (en)
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- Progerin (UniProt# P02545-6) is a truncated version of the lamin A protein involved in the pathology of Hutchinson–Gilford progeria syndrome. Progerin is most often generated by a sporadic single point nucleotide polymorphism c.1824 C>T (GGC -> GGT, p.Gly608Gly) in the gene that codes for matured Lamin A. This mutation activates a cryptic splice site that induces a mutation in premature Lamin A with the deletion of a 50 amino acids group near the C-terminus. The endopeptidase ZMPSTE24 cannot cleave between the missing RSY - LLG amino acid sequence (as seen in the figure) during the maturation of Lamin A, due to the deletion of the 50 amino acids which included that sequence. This leaves the intact premature Lamin A bonded to the methylated carboxyl farnesyl group creating the defective pro (en)
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- Progerina (ca)
- プロジェリン (ja)
- Progerin (en)
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