ライフサイエンスコーパス: AKR1C2

1 AKR1C3 and displays selectivity over AKR1C1/AKR1C2.

2 endogenous AKR1C (AKR1C refers to AKR1C1 and AKR1C2), a target gene of Nrf2.

3 Whereas AKR1C2 acted as a 3alpha-HSD toward 5alpha-DHT, it funct

4 androgen metabolism (HSD3B2, AKR1C3, SRD5A1, AKR1C2, AKR1C1, and UGT2B15).

5 sms in 7 progesterone-related genes (AKR1C1, AKR1C2, AKR1C3, CYP3A4, SRD5A1, SRD5A2, and PGR) influen

6 AKR1C2, also referred to as the human bile acid binder a

7 In HepG2 cells, both AKR1C2 and AKR1C1 (97% sequence homology) were induced b

8 of tissue samples, which paralleled loss of AKR1C2 and AKR1C1 expression.

9 We previously reported the selective loss of AKR1C2 and AKR1C1 in prostate cancers compared with thei

10 the upregulation of cellular stress markers AKR1C2 and AKR1C3 can be quantitatively measured in the

11 tivity of the inducible aldo-keto reductases AKR1C2 and AKR1C3 in living human cells.

12 iciently oxidized by homogeneous recombinant AKR1C2 and AKR1C4.

13 or the increased DHT levels as expression of AKR1C2 and SRD5A2 was reduced in these tumors compared w

14 thway" involving the sequential reactions of AKR1C2 and UGT2B15/17 in prostate.

15 PC-3 cells overexpressing AKR1C2 and, to a lesser extent, AKR1C1 were able to sign

16 everse transcriptase-PCR showed that AKR1C1, AKR1C2, and AKR1C3 transcripts were all expressed.

17 displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1

18 xpression of AKR1C1 and, to a lesser extent, AKR1C2 (but not AKR1C3) decreased progesterone-dependent

19 ells transiently transfected with AKR1C1 and AKR1C2, but not AKR1C3, were able to significantly inhib

20 Suppression of ARK1C1 and AKR1C2 by selective small interfering RNAs inhibited pro

21 The regulation of AKR1C2 by this distal ARE suggests that AKR1C2 detoxifie

22 For rs2854482 in AKR1C2, carrying 1 or 2 A alleles was associated with a

23 ng substrate inhibition was observed for the AKR1C2 catalyzed reduction of tibolone.

24 d the transcriptional activity of the ARE of AKR1C2 comparable with that observed with phase II induc

25 hydrogenase (HSD)/bile acid binding protein (AKR1C2) complexed with NADP(+) and 3alpha,7beta-dihydrox

26 Of these, human AKR1C1 (DD1) and AKR1C2 (DD2) oxidize trans-7,8-dihydroxy-7,8-dihydrobenz

27 ns of ursodeoxycholate, which suggested that AKR1C2 (DD2, bile-acid-binding protein) was not the isof

28 g available crystal structures of AKR1C1 and AKR1C2 demonstrated how 3alpha/3beta-HSD activities are

29 n of AKR1C2 by this distal ARE suggests that AKR1C2 detoxifies products of reactive oxidant injury, w

30 al-time, and operationally simple readout of AKR1C2 enzyme activity in intact mammalian cells.

31 tions using crystal structures of AKR1C1 and AKR1C2 explained why AKR1C2 inverted its stereospecifici

32 Like other members of the superfamily, AKR1C2 folds into an alpha/beta-barrel and binds NADP(+)

33 We speculate that loss of AKR1C1 and AKR1C2 in breast cancer results in decreased progesteron

34 characterization of the proximal promoter of AKR1C2 in HepG2 cell line and the identification of a po

35 We speculate that selective loss of AKR1C2 in prostate cancer promotes clonal expansion of t

36 Suppression of AKR1C1 alone or with AKR1C2 in T-47D cells led to decreased growth in the pre

37 The carboxylate of ursodeoxycholate binds to AKR1C2 in the oxyanion hole at the active site.

38 tructures of AKR1C1 and AKR1C2 explained why AKR1C2 inverted its stereospecificity from a 3alpha-HSD

39 ADPH-dependent reduction of DHT catalyzed by AKR1C2 is 0.033 s(-1).

40 AKR1C2 is implicated in the prostatic production of the

41 ld not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation o

42 experiments to measure the formation of the AKR1C2.NADP(H) binary complex indicated that two slow is

43 The high selectivity of phenyl ketone 1 for AKR1C2 over the many endogenous reductases present in ma

44 large in comparison with those of AKR1C1 and AKR1C2, PGFS (AKR1C3) could catalyze the reduction and/o

45 he ternary structure explains the ability of AKR1C2 to catalyze 3alpha-, 17beta-, and 20alpha-HSD rea

46 The preference for AKR1C1 and AKR1C2 to form 3beta-hydroxytibolone, and the preference

47 rates between null control cells (COS-1) and AKR1C2-transfected cells.

48 No induction of the ARE of AKR1C2 was detected in Nrf2-/- fibroblasts.

49 xcept for the reduction of DhtG catalyzed by AKR1C2, where a complete inversion in stereochemical pre

50 ydrogenase [20alpha-HSD (EC 1.1.1.149)], and AKR1C2, which encodes a 3alpha-hydroxysteroid dehydrogen

51 AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5alpha-dihydrotestosterone.

52 Comparison of the steroid binding pocket of AKR1C2 with that of rat 3alpha-HSD reveals significant d