Linked Life Data

17468497

Source:http://linkedlifedata.com/resource/pubmed/id/17468497

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2007-6-25
pubmed:abstractText
The defective expression of frataxin causes the hereditary neurodegenerative disorder Friedreich's ataxia (FRDA). Human frataxin is synthesized as a 210 amino acid precursor protein, which needs proteolytic processing into mitochondria to be converted into the functional mature form. In vitro processing of human frataxin was previously described to yield a 155 amino acid mature form, corresponding to residues 56-210 (frataxin(56-210)). Here, we studied the maturation of frataxin by in vivo overexpression in human cells. Our data show that the main form of mature frataxin is generated by a proteolytic cleavage between Lys80 and Ser81, yielding a 130 amino acid protein (frataxin(81-210)). This maturation product corresponds to the endogenous frataxin detected in human heart, peripheral blood lymphocytes or dermal fibroblasts. Moreover, we demonstrate that frataxin(81-210) is biologically functional, as it rescues aconitase defects in frataxin-deficient cells derived from FRDA patients. Importantly, our data indicate that frataxin(56-210) can be produced in vivo when the primary 80-81 maturation site is unavailable, suggesting the existence of proteolytic mechanisms that can actively control the size of the mature product, with possible functional implications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1534-40
pubmed:dateRevised
2010-3-2
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
In vivo maturation of human frataxin.
pubmed:affiliation
Laboratory of Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Rome, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't