Linked Life Data

20457756

Source:http://linkedlifedata.com/resource/pubmed/id/20457756

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-6-10
pubmed:abstractText
Small ubiquitin-like modifier (SUMO) modification of proteins (SUMOylation) and deSUMOylation have emerged as important regulatory mechanisms for protein function. SENP1 (SUMO-specific protease) deconjugates SUMOs from modified proteins. We have created SENP1 knockout (KO) mice based on a Cre-loxP system. Global deletion of SENP1 (SENP1 KO) causes anemia and embryonic lethality between embryonic day 13.5 and postnatal day 1, correlating with erythropoiesis defects in the fetal liver. Bone marrow transplantation of SENP1 KO fetal liver cells to irradiated adult recipients confers erythropoiesis defects. Protein analyses show that the GATA1 and GATA1-dependent genes are down-regulated in fetal liver of SENP1 KO mice. This down-regulation correlates with accumulation of a SUMOylated form of GATA1. We further show that SENP1 can directly deSUMOylate GATA1, regulating GATA1-dependent gene expression and erythropoiesis by in vitro assays. Moreover, we demonstrate that GATA1 SUMOylation alters its DNA binding, reducing its recruitment to the GATA1-responsive gene promoter. Collectively, we conclude that SENP1 promotes GATA1 activation and subsequent erythropoiesis by deSUMOylating GATA1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1540-9538
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
207
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1183-95
pubmed:dateRevised
2011-3-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
SENP1-mediated GATA1 deSUMOylation is critical for definitive erythropoiesis.
pubmed:affiliation
Interdepartmental Program in Vascular Biology and Therapeutics, Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural