The alternate N-terminal sequence of rat androgen-binding protein/sex hormone-binding globulin contains a nuclear targeting signal.
Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an extracellular carrier protein of androgens and estrogens. The protein regulates the bioavailability of sex steroids, and expanding evidence suggests that it also acts as a hormone. ABP/SHBG is secreted by Sertoli cells and hepatocytes using a signal peptide. An alternate messenger RNA encodes a nonsecreted form of ABP/SHBG (Alt-ABP/SHBG) that has a unique N-terminal amino acid sequence. In this study, we report that the alternate N-terminal sequence targets Alt-ABP/SHBG to the nucleus instead of the endoplasmic reticulum. The recombinant Alt-ABP/SHBG expressed in COS-7 cells was located in the nucleus, whereas recombinant cellular ABP/SHBG was primarily cytoplasmic. Neither dihydrotestosterone nor estradiol had any detectable effect on the ABP/SHBG or Alt-ABP/SHBG cellular location. Although the function of the nuclear Alt-ABP/SHBG is unknown, it may act as a modulator of androgen receptor- and/or estrogen receptor-mediated gene regulation.
Joseph
D R
DR
Department of Pediatrics, University of North Carolina, Chapel Hill, 27599, USA.
Becchis
M
M
Fenstermacher
D A
DA
Petrusz
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018014:Gene Transfer Techniques; D008969:Molecular Sequence Data; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000235:genetics* / Q000378:metabolism
D011994:Recombinant Proteins; D012738:Sex Hormone-Binding Globulin