ライフサイエンスコーパス: P450c17

1 bovine 17alpha-hydroxylase/17,20-lyase P450 (P450c17).

2 t p38beta, conferred 17,20 lyase activity on P450c17.

3 vity of P450c17, and 17,20 lyase activity of P450c17.

4 vity, and support of 17,20 lyase using human P450c17.

5 ase and 17,20-lyase activities of cytochrome P450c17.

6 , enhances lyase activities of rat and human P450c17.

7 oes not require electron transfer from b5 to P450c17.

8 tution mutations in CYP17, the gene encoding P450c17.

9 [5-6 mol of 17alpha-OH-progesterone (mol of P450c17)-1 min-1] was achieved using a large molar exces

10 The steroid hydroxylases CYP17A1 (P450c17, 17-hydroxylase/17,20-lyase) and CYP21A2 (P450c2

11 ymes crucial for their synthesis, especially P450c17 (17alpha-hydroxylase/c17,20 lyase), are expresse

12 Cytochrome P450c17, a steroidogenic enzyme encoded by the CYP17A1 g

13 icant inhibition (>50%) of Fpr-Fld-supported P450c17 activity while much higher ionic strength (300 m

14 We therefore determined if products of P450c17 activity, DHEA and DHEAS, regulated the motility

15 ns with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyperandrogenism.

16 resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycyst

17 zed that hyperinsulinemia stimulates ovarian P450c17 alpha activity.

18 P450c17 alpha, which is involved in androgen biosynthesi

19 ctions 5-fold; coexpression of human b5 with P450c17 also increases the Vmax of the 17,20-lyase react

20 estigate potential actions of these drugs on P450c17 and 3betaHSDII, we used "humanized yeast" that e

21 direct but weaker inhibitory effects on both P450c17 and 3betaHSDII.

22 Antiserum to P450c17 co-immunoprecipitated P450c17 and both p38 isoforms; however, knockdown of p38

23 obably by increasing the interaction between P450c17 and NADPH-cytochrome P450 oxidoreductase.

24 chrome c to microsomes containing both human P450c17 and OR demonstrate that the stimulatory action o

25 to microsomes from yeast coexpressing human P450c17 and OR, further increases the Vmax of the 17,20-

26 Simultaneous expression of human b5 with P450c17 and OR, or addition of purified human b5 to micr

27 ection of non-steroidogenic COS-1 cells with P450c17 and p38 expression vectors showed that p38alpha,

28 l adrenal hyperplasia with apparent combined P450C17 and P450C21 deficiency in affected children.

29 l adrenal hyperplasia with apparent combined P450C17 and P450C21 deficiency is associated with accumu

30 important in electron transfer from NADPH to P450C17 and P450C21.

31 P450scc is more abundant than mRNA for both P450c17 and steroidogenic factor 1 in sebaceous glands a

32 We have shown that serine phosphorylation of P450c17 and the allosteric action of cytochrome b5 incre

33 chrome P450 17alpha-hydroxylase/17,20-lyase (P450c17) and donates electrons to this enzyme when recon

34 n reductase, cytochrome P450 17-hydroxylase (P450c17), and steroidogenic factor 1 was documented in h

35 on of NADPH, 17alpha-hydroxylase activity of P450c17, and 17,20 lyase activity of P450c17.

36 ed by a single enzyme, microsomal cytochrome P450c17, and because the index case of apparent isolated

37 The relative abundance of mRNA for P450scc, P450c17, and steroidogenic factor 1 in SEB-1 sebocytes a

38 PP2A but not PP4 coimmunoprecipitated with P450c17, and suppression of PP2A by small interfering RN

39 Rat and human forms of P450c17 are 69% identical at the amino acid level.

40 Even though orthologous forms of P450c17 are capable of catalyzing the same enzymatic act

41 based on the report that recombinant bovine P450c17 can be functionally active in live bacteria.

42 0 17A1 (also known as CYP17A1 and cytochrome P450c17) catalyses the biosynthesis of androgens in huma

43 Cytochrome P450c17 catalyzes 17 alpha-hydroxylation needed for cort

44 Whether or not P450c17 catalyzes 17,20 lyase activity is determined by

45 Cytochrome P450c17 catalyzes the 17alpha-hydroxylase activity requi

46 pha-hydroxylase/17,20-lyase cytochrome P450 (P450c17) catalyzes both the 17alpha-hydroxylase reaction

47 Antiserum to P450c17 co-immunoprecipitated P450c17 and both p38 isofo

48 Cytochrome P450c17 (CYP17) catalyzes both the 17alpha-hydroxylase a

49 Cytochrome p450c17 (CYP17) converts the C21 steroids pregnenolone a

50 ating the 17,20-lyase activity of cytochrome P450c17 (CYP17A1).

51 Critical Fld-P450c17 electrostatic interactions are disrupted at mode

52 tic acid releasing assay and utilized intact P450c17-expressing E. coli for the source of the enzyme.

53 nenolone at a constant rate failed to rescue P450c17(-/-) fetuses.

54 We deleted the mouse P450c17 gene in 127/SvJ mice and obtained several lines

55 the two forms of P450c17 indicate that human P450c17 has evolved as an enzyme system that limits andr

56 Yeast expressing only P450c17 have 17alpha-hydroxylase and trace 17,20-lyase a

57 These data suggest that steroid products of P450c17 have heretofore-unknown essential functions in e

58 We expressed human P450c17, human P450-oxidoreductase (OR), and/or human cy

59 nce the relative catalytic efficiency of the P450c17 hydroxylase and lyase reactions.

60 regulating the lyase activity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its hydroxyla

61 p38alpha phosphorylates P450c17 in a fashion that confers increased 17,20 lyase

62 Immunocytochemistry identified P450c17 in embryonic endoderm in E7 wild-type and hetero

63 serves as the predominant electron donor to P450c17 in reconstitution assays.

64 e differences in physiological roles between P450c17 in these two species, it could be predicted that

65 ments the 17,20-lyase activity of cytochrome P450c17 in vitro, but this has not been demonstrated in

66 Coexpression of human OR with P450c17 increases the Vmax of both the 17alpha-hydroxyla

67 chemical properties between the two forms of P450c17 indicate that human P450c17 has evolved as an en

68 0 oxidoreductase, the electron donor used by P450c17, indicated that the mutants had a diminished abi

69 nduced formation of D was not blocked by the P450c17 inhibitor, SU-10603.

70 iable, and reproducible method for screening P450c17 inhibitors.

71 hrome P450 17alpha-hydroxylase-C17,20-lyase (P450c17) inhibitors with the aim of inhibiting androgen

72 teric action of cytochrome b5 to promote POR-P450c17 interaction, and Ser/Thr phosphorylation of P450

73 f P450c17, which also appears to promote POR-P450c17 interaction.

74 NaCl) is required to disrupt P450 reductase-P450c17 interactions to the same extent.

75 In other species including humans, P450c17 is expressed in both adrenal and gonads and part

76 corticosterone as the major glucocorticoid, P450c17 is expressed predominantly in the gonads, and is

77 es, but the ratio of these two activities of P450c17 is regulated post-translationally.

78 In the biosynthesis of steroid hormones, P450c17 is the single enzyme that catalyzes both the 17a

79 The kinase(s) that phosphorylates P450c17 is unknown.

80 25.4 +/- 5.1 microm) and both activities of P450c17 (K(I) for 17alpha-hydroxylase, 8.4 +/- 0.6 micro

81 We hypothesized that P450c17-knockout mice would have disordered sex steroid

82 using a large molar excess (50-100-fold over P450c17) of a 1:1 ratio of Fpr-Fld, although this rate w

83 c effector that interacts primarily with the P450c17.OR complex to stimulate 17, 20-lyase activity.

84 Increasing P450c17 phosphorylation could compensate for this reduce

85 ytochrome b5 are independent of the state of P450c17 phosphorylation.

86 t both P450 reductase- and Fpr-Fld-supported P450c17 progesterone 17alpha-hydroxylase activity while

87 significantly decreased flavodoxin-supported P450c17 progesterone 17alpha-hydroxylase activity.

88 roduction to the gonads where a favorable b5:P450c17 ratio exists.

89 When expressed in bacteria, human P450c17 required either cytochrome b5 or phosphorylation

90 Serine phosphorylation of P450c17 specifically increases 17,20 lyase activity, but

91 Computer-graphic modelling of P450c17 suggests that both mutations lie in or near the

92 bind with equal or even greater affinity to P450c17 than wild-type Fld.

93 One region of embryonic expression of P450c17, the neocortical subplate, has been postulated t

94 were based on POR's support of catalysis by P450c17--the enzyme most closely associated with the hor

95 ect to their electrostatic interactions with P450c17, their ability to support maximal P450c17 turnov

96 both the hydroxylase and lyase activities of P450c17 to the same proportional extent (hydroxylase-to-

97 Maximum P450c17 turnover [5-6 mol of 17alpha-OH-progesterone (mo

98 th P450c17, their ability to support maximal P450c17 turnover, and the FMN redox states (one-electron

99 The action of troglitazone on P450c17 was competitive, but it was mainly a noncompetit

100 ochemical activity of cytochrome P450scc and P450c17 was demonstrated in SEB-1 sebocytes using radioi

101 On the other hand, P450c17 was not detected.

102 Bacterially expressed human P450c17 was phosphorylated by p38alpha in vitro at a non

103 ein, 3beta-hydroxysteroid dehydrogenase, and P450c17) was impaired.

104 artially purified, recombinant human and rat P450c17, we found that the most significant differences

105 biosynthetic enzymes (p450scc, 3betaHSD and p450c17) were not expressed in XY Fog2(-/-) and Gata(ki/

106 interaction, and Ser/Thr phosphorylation of P450c17, which also appears to promote POR-P450c17 inter

107 ocorticoids and mineralocorticoids, requires P450c17, which catalyzes both 17 alpha-hydroxylase and 1

108 productively normal, but in all mouse lines, P450c17(-/-) zygotes died by embryonic day 7, prior to g