The transactivation-competent carboxyl-terminal domain of AF-9 is expressed within a sexually dimorphic transcript in rat pituitary.
We have investigated the biological role of the cellular counterpart of the leukemogenic AF-9 gene by cloning the rat AF-9 (rAF-9) cDNA and defining the regulation of an anterior pituitary-specific rAF-9 transcript that is expressed in a sexually dimorphic manner. Expression of this transcript is down-regulated after puberty in females and can be subsequently up-regulated in adults by ovariectomy. Hormone replacement studies have provided direct evidence that rAF-9 mRNA expression is suppressed by estrogen. Mapping the 1.9 kb anterior pituitary transcript has shown that it corresponds in size to the rAF-9 cDNA clone, which contains an open reading frame (ORF) that is truncated compared with the human AF-9 ORF, but encodes a previously defined transcriptional activation domain. Thus, the cellular AF-9 gene is alternatively expressed in a manner that reflects the presence of translocated, functionally active (oncogenic) AF-9 sequences in leukemias. Using a novel antisera raised against a rAF-9 peptide, we have also demonstrated tissue- and sex-specific expression of a nuclear 41 kDa anterior pituitary protein and have localized this protein to a major population of growth hormone synthesizing cells. By localizing the expression and defining the physiological regulation of rAF-9, our studies have provided novel insights into the AF-9 gene that will facilitate an understanding of both oncogenic and endocrine roles.
Morgan
H
H
School of Biosciences, Cardiff University, Cardiff CF1 3US. U.K.
Smith
M
M
Burke
Z
Z
Carter
D
D
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry; D003001:Cloning, Molecular; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009919:Orchiectomy; D009928:Organ Specificity; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D012727:Sex Characteristics; D015533:Transcriptional Activation
C489901:MLLT3 protein, human; C489903:Mllt3 protein, rat; D009687:Nuclear Proteins; D012333:RNA, Messenger