Linked Life Data

12149273

Source:http://linkedlifedata.com/resource/pubmed/id/12149273

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
40
pubmed:dateCreated
2002-9-30
pubmed:abstractText
Myeloid cell leukemia 1 protein (MCL1) is an anti-apoptotic protein that is structurally related to Bcl-2. Unlike other Bcl-2 family proteins that are constitutively expressed, MCL1 is inducibly expressed in cells that are recently exposed to growth and differentiation stimuli. Here, we report the identification of fortilin as a novel MCL1-interacting protein by screening of a yeast two-hybrid library with MCL1 as bait. Fortilin specifically interacted with MCL1 both in vitro and in vivo. The intracellular localization of fortilin was predominantly nuclear and identical to that of MCL1, as shown by immunostaining and confocal microscopy analysis. Fortilin, like MCL1, was rapidly inducible in serum-stimulated human aortic vascular smooth muscle cells. Although the depletion of intracellular fortilin by small interfering RNA (siRNA) against fortilin (siRNA-fortilin) did not affect intracellular MCL1 level, the depletion of intracellular MCL1 by siRNA-MCL1 was associated with the significant reduction of the fortilin protein level, without affecting the fortilin transcript numbers. In addition, a pulse-chase experiment showed that the depletion of MCL1 by siRNA-MCL1 was associated with the rapid degradation of fortilin protein, which was found quite stable in the presence of MCL1. Furthermore, the half-life of fortilin(R21A), a point mutant of fortilin lacking the binding to MCL1, was significantly shorter than that of wild-type fortilin as shown by a pulse-chase experiment. These data suggest that MCL1, in addition to being an anti-apoptotic molecule, serves as a chaperone of fortilin, binding and stabilizing fortilin in vivo. Taken together with our previous observation that fortilin overexpression prevents cells from undergoing apoptosis (Li, F., Zhang, D., and Fujise, K. (2001) J. Biol. Chem. 276, 47542-47549), it is likely that MCL1, an anti-apoptotic protein inducible by growth and differentiation stimuli, stabilizes another anti-apoptotic protein fortilin maximizing the prosurvival environment in cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37430-8
pubmed:dateRevised
2008-7-9
pubmed:meshHeading
pubmed-meshheading:12149273-Animals, pubmed-meshheading:12149273-Apoptosis, pubmed-meshheading:12149273-Binding Sites, pubmed-meshheading:12149273-Bone Neoplasms, pubmed-meshheading:12149273-Cell Differentiation, pubmed-meshheading:12149273-Cell Division, pubmed-meshheading:12149273-Cloning, Molecular, pubmed-meshheading:12149273-Gene Library, pubmed-meshheading:12149273-Humans, pubmed-meshheading:12149273-Mutagenesis, pubmed-meshheading:12149273-Neoplasm Proteins, pubmed-meshheading:12149273-Nuclear Proteins, pubmed-meshheading:12149273-Osteosarcoma, pubmed-meshheading:12149273-Polymerase Chain Reaction, pubmed-meshheading:12149273-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12149273-Recombinant Proteins, pubmed-meshheading:12149273-Sequence Deletion, pubmed-meshheading:12149273-Transfection, pubmed-meshheading:12149273-Tumor Cells, Cultured, pubmed-meshheading:12149273-Tumor Markers, Biological
pubmed:year
2002
pubmed:articleTitle
Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and Fortilin. The potential role of MCL1 as a fortilin chaperone.
pubmed:affiliation
Research Center for Cardiovascular Diseases, Institute of Molecular Medicine for the Prevention of Human Diseases, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't