Linked Life Data

10579309

Source:http://linkedlifedata.com/resource/pubmed/id/10579309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-12-20
pubmed:abstractText
The majority of ovarian follicles undergo atresia mediated by apoptosis. Bcl-2-related proteins act as regulators of apoptosis via the formation of dimers with proteins inside and outside the Bcl-2 family. Previous studies have identified BAD as a proapoptotic Bcl-2 family member expressed in the ovary. It is known that BAD phosphorylation induced by survival factors leads to its preferential binding to 14-3-3 and suppression of the death-inducing function of BAD. To identify ovarian binding partners for hypophosphorylated BAD, we performed a yeast two-hybrid screening of a rat ovary complementary DNA library using as bait a mutant BAD incapable of binding to 14-3-3. Screening of yeast transformants yielded positive clones encoding the rat ortholog of Mcl-1 (myeloid cell leukemia-1), an antiapoptotic Bcl-2 protein. Amino acid sequence analysis revealed that rat and human Mcl-1 showed a complete conservation of the Bcl-2 homology domains BH1, BH2, and BH3. In the yeast two-hybrid system, Mcl-1 binds to the hypophosphorylated mutant of BAD and interacts preferentially with different proapoptotic (Bax, Bak, Bok, Bik, and BOD) compared with antiapoptotic Bcl-2 family members (Bcl-2, Bcl-xL, Bcl-w, Bfl-1, CED-9, and BHRF-1). Northern blot hybridization demonstrated expression of Mcl-1 transcripts of 2.3 and 3.7 kb in the ovary and diverse other rat tissues. In immature rats, PMSG treatment led to a transient increase in the 2.3-kb Mcl-1 transcript, peaking at 6 h after injection and returning to baseline levels after 24 h. Moreover, the same transcript was induced in the PMSG-primed preovulatory rat ovary 6 h after the administration of ovulatory doses of either hCG or FSH. In situ hybridization studies revealed that the gonadotropin stimulation of ovarian Mcl-1 message occurs in both granulosa and thecal cells. In conclusion, rat Mcl-1 was identified as an ovarian BAD-interacting protein and the message for the antiapoptotic Mcl-1 protein was induced after treatment with gonadotropins in granulosa and thecal cells of growing follicles.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5469-77
pubmed:dateRevised
2008-7-9
pubmed:meshHeading
pubmed-meshheading:10579309-Amino Acid Sequence, pubmed-meshheading:10579309-Animals, pubmed-meshheading:10579309-Apoptosis, pubmed-meshheading:10579309-Blotting, Northern, pubmed-meshheading:10579309-Chickens, pubmed-meshheading:10579309-Chorionic Gonadotropin, pubmed-meshheading:10579309-Dimerization, pubmed-meshheading:10579309-Female, pubmed-meshheading:10579309-Follicle Stimulating Hormone, pubmed-meshheading:10579309-Gene Expression, pubmed-meshheading:10579309-Gonadotropins, pubmed-meshheading:10579309-Granulosa Cells, pubmed-meshheading:10579309-Humans, pubmed-meshheading:10579309-In Situ Hybridization, pubmed-meshheading:10579309-Molecular Sequence Data, pubmed-meshheading:10579309-Neoplasm Proteins, pubmed-meshheading:10579309-Ovary, pubmed-meshheading:10579309-Ovulation, pubmed-meshheading:10579309-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:10579309-RNA, Messenger, pubmed-meshheading:10579309-Rats, pubmed-meshheading:10579309-Rats, Sprague-Dawley, pubmed-meshheading:10579309-Sequence Homology
pubmed:year
1999
pubmed:articleTitle
Characterization of the antiapoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) and the stimulation of its message by gonadotropins in the rat ovary.
pubmed:affiliation
Department of Gynecology and Obstetrics, Stanford University Medical Center, California 94305-5317, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't