Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Blocking protein farnesyl… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Kontaktformulär








 


OBS! Vill du ha svar, ange e-post eller telefonnummer!




Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation

Artikel i vetenskaplig tidskrift
Författare S. H. Yang
Martin Bergö
J. I. Toth
X. Qiao
Y. Hu
S. Sandoval
M. Meta
P. Bendale
M. H. Gelb
S. G. Young
L. G. Fong
Publicerad i Proc Natl Acad Sci U S A
Volym 102
Nummer/häfte 29
Sidor 10291-10296
Publiceringsår 2005
Publicerad vid Institutionen för invärtesmedicin
Sidor 10291-10296
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämnesord CAAX proteiner, djurmodeller, genteknik, prelamin A
Ämneskategorier Molekylär medicin

Sammanfattning

Hutchinson-Gilford progeria syndrome (HGPS), a progeroid syndrome in children, is caused by mutations in LMNA (the gene for prelamin A and lamin C) that result in the deletion of 50 aa within prelamin A. In normal cells, prelamin A is a "CAAX protein" that is farnesylated and then processed further to generate mature lamin A, which is a structural protein of the nuclear lamina. The mutant prelamin A in HGPS, which is commonly called progerin, retains the CAAX motif that triggers farnesylation, but the 50-aa deletion prevents the subsequent processing to mature lamin A. The presence of progerin adversely affects the integrity of the nuclear lamina, resulting in misshapen nuclei and nuclear blebs. We hypothesized that interfering with protein farnesylation would block the targeting of progerin to the nuclear envelope, and we further hypothesized that the mislocalization of progerin away from the nuclear envelope would improve the nuclear blebbing phenotype. To approach this hypothesis, we created a gene-targeted mouse model of HGPS, generated genetically identical primary mouse embryonic fibroblasts, and we then examined the effect of a farnesyltransferase inhibitor on nuclear blebbing. The farnesyltransferase inhibitor mislocalized progerin away from the nuclear envelope to the nucleoplasm, as determined by immunofluoresence microscopy, and resulted in a striking improvement in nuclear blebbing (P < 0.0001 by chi(2) statistic). These studies suggest a possible treatment strategy for HGPS.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?

Denna text är utskriven från följande webbsida:
http://gu.se/forskning/publikation/?feedbackForm=true&returnAddress=http%3A%2F%2Fgu.se%2Fforskning%2Fpublikation%2F%3Fprint%3Dtrue%26siteMap%3Dtrue%26publicationId%3D55196&recipientName=Webbredaktion&encodedEmail=YWxsYW4uZXJpa3Nzb25AZ3Uuc2U&publicationId=55196
Utskriftsdatum: 2020-08-05