Linked Life Data

17594238

Source:http://linkedlifedata.com/resource/pubmed/id/17594238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-6-27
pubmed:abstractText
Ubiquitin-mediated proteolysis plays a critical role in the degradation of proteins important in the cellular processes, such as cell cycle/division, differentiation and development, DNA repair, transcriptional regulation, and signaling. It is carried out by a complex cascade of enzymes that contain a high degree of specificity to motifs found in many proteins with rapid turnover. For example, the PEST motifs are hydrophilic stretches of amino acids that serve as signals for proteolytic degradation. In this study, we propose that amino acid altering non-synonymous single nucleotide polymorphisms (nsSNP) result in the abolishment or creation of putative PEST motifs, and thus lead to abnormal stabilization or degradation of the proteins. Using a web-based algorithm, PESTFind, we analyzed a total of 253 nsSNPs from proteins involved in cell cycle (n = 24), DNA repair (n = 128), and TGFbeta signaling pathway (n = 101). Fifteen nsSNPs were located within putative PEST sequences, and 9/15 (60%) either created or abolished these PEST motifs. PEST motifs were abolished in the presence of nsSNPs in CCND3, PMS2, POLE4, SITPEC, and PPARG and putative PEST motifs were created in NEIL2, BIRC4, MLL2, and PPP1R15A. Although experimental analyses are required to confirm these results, they suggest that nsSNPs can induce changes in ubiquitin-mediated protein degradation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1536-2310
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
200-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Human non-synonymous single nucleotide polymorphisms can influence ubiquitin-mediated protein degradation.
pubmed:affiliation
Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't