Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

Ariyoshi, Noritaka; Kim, Young Cheul; Artemenko, Irina; Bhattacharyya, K K; Jefcoate, Colin R.

doi:10.1074/jbc.273.13.7610

Cited by 81 publications

(28 citation statements)

References 58 publications

(75 reference statements)

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“…It is also possible that TIS11b participates in the control of the stability of many other ACTH target genes. For example, the gene encoding StAR (Steroidogenesis Acute Regulatory protein), a mitochondrial protein essential for cholesterol transfer to the inner mitochondrial membrane, is a likely candidate as its expression is rapidly and transiently induced by ACTH in adrenocortical cells (Brand et al, 1998) and since several AREs are present in its mRNA 3 0 -UTR (Ariyoshi et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Destabilization of vascular endothelial growth factor mRNA by the zinc-finger protein TIS11b

et al. 2004

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Section: Discussionmentioning

confidence: 99%

Destabilization of vascular endothelial growth factor mRNA by the zinc-finger protein TIS11b

et al. 2004

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“…Oligonucleotides used for reverse transcription-polymerase chain reaction (RT-PCR) were custom-ordered from Life Technologies, Inc. PCR primer pairs were selected from different exons of the corresponding genes to discriminate PCR products that might arise from possible chromosome DNA contaminants. Specifically, they were derived from the cDNA clones at the following nucleotide numbers: 1651-1670 and 1751-1770 for steroidogenic acute regulatory protein (StAR) (20); 148 -167 and 637-656 for P450scc (21); 860 -879 and 1062-1079 for P450arom (22); 487-505 and 942-959 for FSH-R (23); 166 -185 and 345-366 for inhibin ␣-subunit; 428 -447 and 588 -607 for inhibin/activin ␤A-subunit; 32-51 and 239 -258 for inhibin/activin ␤B-subunit (24); 962-981 and 1401-1420 for LH-R (25); and 401-421 and 575-595 for ribosomal RNA protein-L19 (L19) (26). The steady state levels of mRNA encoding the key steroidogenic factors, StAR, P450scc, P450arom, and FSH-R (referred to "target" mRNA), were analyzed by quantitative competitive RT-PCR as we reported previously (17).…”

Section: Rna Extraction and Analysis By Quantitative Competitive Rt-pmentioning

confidence: 99%

Biological Function and Cellular Mechanism of Bone Morphogenetic Protein-6 in the Ovary

Otsuka

Moore

Shimasaki

2001

Journal of Biological Chemistry

184

129

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The process of ovarian folliculogenesis is composed of proliferation and differentiation of the constitutive cells in developing follicles. Growth factors emitted by oocytes integrate and promote this process. Growth differentiation factor-9 (GDF-9), bone morphogenetic protein (BMP)-15, and BMP-6 are oocyte-derived members of the transforming growth factor-␤ superfamily. In contrast to the recent studies on GDF-9 and BMP-15, nothing is known about the biological function of BMP-6 in the ovary. Here we show that, unlike BMP-15 and GDF-9, BMP-6 lacks mitogenic activity on rat granulosa cells (GCs) and produces a marked decrease in folliclestimulating hormone (FSH)-induced progesterone (P 4 ) but not estradiol (E 2 ) production, demonstrating not only the first identification of GCs as BMP-6 targets in the ovary but also its selective modulation of FSH action in steroidogenesis. This BMP-6 activity resembles BMP-15 but differs from GDF-9 activities. BMP-6 also exhibited similar action to BMP-15 by attenuating the steady state mRNA levels of FSH-induced steroidogenic acute regulatory protein (StAR) and P450 side-chain cleavage enzyme (P450scc), without affecting P450 aromatase mRNA level, supporting its differential function on FSH-regulated P 4 and E 2 production. However, unlike BMP-15, BMP-6 inhibited forskolin-but not 8-bromo-cAMP-induced P 4 production and StAR and P450scc mRNA expression. BMP-6 also decreased FSH-and forskolin-stimulated cAMP production, suggesting that the underlying mechanism by which BMP-6 inhibits FSH action most likely involves the down-regulation of adenylate cyclase activity. This is clearly distinct from the mechanism of BMP-15 action, which causes the suppression of basal FSH receptor (FSH-R) expression, without affecting adenylate cyclase activity. As assumed, BMP-6 did not alter basal FSH-R mRNA levels, whereas it inhibited FSH-and forskolin-but not 8-bromo-cAMPinduced FSH-R mRNA accumulation. These studies provide the first insight into the biological function of BMP-6 in the ovary and demonstrate its unique mechanism of regulating FSH action.

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“…In a previous study (32), we showed that ACTH maximally stimulated steroid synthesis in rats in vivo within 10 min, without any measurable change in multiple forms of total StAR. In this paper, we address the question of whether mitochondrial processing is, indeed, essential for activated adrenal cholesterol metabolism, despite the evident possibility of extramitochondrial StAR activity.…”

mentioning

confidence: 99%

“…This trophic hormone-dependent transport of cholesterol from mitochondrial outer membrane to inner membrane (4,7,8) is blocked in vivo within 10 min by protein synthesis inhibitors, such as cycloheximide (CHX) (9,10). A series of cAMP-stimulated and CHX-sensitive phosphoproteins (30)(31)(32)(33)(34)(35)(36)(37), which localize to the mitochondria, have been identified in cultured adrenal and testis cells (11)(12)(13)(14)(15)(16)(17). The gene that encodes these proteins has been cloned, and the active form has been named the steroidogenic acute regulatory protein (StAR) (18).…”

mentioning

confidence: 99%

Mitochondrial Processing of Newly Synthesized Steroidogenic Acute Regulatory Protein (StAR), but Not Total StAR, Mediates Cholesterol Transfer to Cytochrome P450 Side Chain Cleavage Enzyme in Adrenal Cells

Artemenko

Zhao

Hales³

et al. 2001

Journal of Biological Chemistry

Self Cite

196

151

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The metabolism of cholesterol by cytochrome P450 side chain cleavage enzyme is hormonally regulated in steroidogenic tissues via intramitochondrial cholesterol transport. The mediating steroidogenic acute regulatory protein (StAR) is synthesized as a 37-kDa (p37) precursor that is phosphorylated by protein kinase A and cleaved within the mitochondria to generate 30-kDa forms (p30, pp30). The effectiveness of modified recombinant StAR forms in COS-1 cells without mitochondrial import has led to a prevailing view that cholesterol transport is mediated by p37 StAR via activity on the outer mitochondrial membrane. The present study of the activation of cholesterol metabolism by bromo-cAMP in adrenal cells in relation to 35 S-StAR turnover indicates that targeting of pp30 to the inner membrane provides the dominant cholesterol transport mechanism. We show that 1) only newly synthesized StAR is functional, 2) phosphorylation and processing of p37 to pp30 occurs rapidly and stoichiometrically, 3) both steps are necessary for optimum transport, and 4) newly synthesized pp30 exhibits very high activity (400 molecules of cholesterol/StAR/min). Segregation of cAMP activation and synthesis of StAR from cholesterol metabolism showed that very low levels of newly synthesized StAR (1 fmol/min/10 6 cells) sustained activated cholesterol metabolism (0.4 pmol/min/10 6 cells, t1 ⁄2 ‫؍‬ 70 min) long after complete removal of p37 (t1 ⁄2 ‫؍‬ 5 min). This activity was highly sensitive to inhibition of processing by CCCP only until sufficient pp30 was formed. Maximum activation preceded bromo-cAMP-induced StAR expression, indicating other limiting steps in cholesterol metabolism.The conversion of cholesterol to pregnenolone, the first step in steroid synthesis, is catalyzed by cytochrome P450 side chain cleavage enzyme (P450scc), 1 which is localized on the matrix side of the inner mitochondrial membrane (1, 2). The transfer of cholesterol to P450scc, a limiting step in this conversion (3, 4), requires hormonal activation of cholesterol mobilization to the mitochondria. This mobilization is dependent on the uptake of lipoproteins, lysosomal-cytosolic transfer, and hydrolysis of cholesterol esters as well as on two subsequent transfer steps (5). The first step involves transfer of cholesterol to the mitochondria and is dependent on an intact cytoskeleton but not on protein synthesis (6). The second step involves transfer within the mitochondria from outer to inner membrane. This trophic hormone-dependent transport of cholesterol from mitochondrial outer membrane to inner membrane (4, 7, 8) is blocked in vivo within 10 min by protein synthesis inhibitors, such as cycloheximide (CHX) (9, 10). A series of cAMP-stimulated and CHX-sensitive phosphoproteins (30 -37 kDa), which localize to the mitochondria, have been identified in cultured adrenal and testis cells (11)(12)(13)(14)(15)(16)(17). The gene that encodes these proteins has been cloned, and the active form has been named the steroidogenic acute regulatory protein (StAR) (18). The exp...

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Characterization of the Rat Star Gene That Encodes the Predominant 3.5-Kilobase Pair mRNA

Cited by 81 publications

References 58 publications

Destabilization of vascular endothelial growth factor mRNA by the zinc-finger protein TIS11b

Destabilization of vascular endothelial growth factor mRNA by the zinc-finger protein TIS11b

Biological Function and Cellular Mechanism of Bone Morphogenetic Protein-6 in the Ovary

Mitochondrial Processing of Newly Synthesized Steroidogenic Acute Regulatory Protein (StAR), but Not Total StAR, Mediates Cholesterol Transfer to Cytochrome P450 Side Chain Cleavage Enzyme in Adrenal Cells

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