Linked Life Data

21418451

Source:http://linkedlifedata.com/resource/pubmed/id/21418451

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-5-10
pubmed:abstractText
Taspase1 is a threonine protease suspected to process (patho)biologically relevant nuclear and cytoplasmic substrates, such as the mixed lineage leukemia protein. However, neither the mechanisms regulating Taspase1's intracellular localization nor their functional consequences are known. Analysis of endogenous and ectopically expressed Taspase1 detected the protease predominantly in the nucleus accumulating at the nucleolus. Microinjection and ectopic expression studies identified an evolutionarily conserved bipartite nuclear import signal (NLS) (amino acids (197) KRNKRKLELA ERVDTDFMQLKKRR(220) ) interacting with importin-?. Notably, an NLS-mutated, import-deficient Taspase1 was biologically inactive. Although the NLS conferred nuclear transport already of the proenzyme, Taspase1's nucleolar localization required its autoproteolytic processing, triggering its interaction with the nucleolar shuttle protein nucleophosmin. In contrast, (auto)catalytically inactive Taspase1 mutants neither accumulated at the nucleolus nor bound nucleophosmin. Active nuclear import and interaction with nucleophosmin was found to be required for the formation of proteolytically active Taspase1 ensuring to efficiently process its nuclear targets. Intriguingly, coexpression of pathological nucleophosmin variants increased the amount of cytoplasmic Taspase1. Hence, Taspase1 appears to exploit the nuclear export activity of nucleophosmin to gain transient access to the cytoplasm required to also cleave its cytoplasmic substrates. Collectively, we here describe a hitherto unknown mechanism regulating the biological activity of this protease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1600-0854
pubmed:author
pubmed:copyrightInfo
© 2011 John Wiley & Sons A/S.
pubmed:issnType
Electronic
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
703-14
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The importin-alpha/nucleophosmin switch controls taspase1 protease function.
pubmed:affiliation
Molecular and Cellular Oncology/Mainz Screening Center, University Hospital of Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't