ライフサイエンスコーパス: PEPD

1 PEPD binds to the proline-rich domain in p53, which inhi

2 PEPD differs from all known EGFR ligands in that it does

3 PEPD mutations also increase resurgent currents, which i

4 PEPD mutations impair Nav1.7 fast inactivation and incre

5 PEPD mutations in the putative inactivation gate have be

6 The Nav1.7 PEPD mutations are located in regions of the channel sug

7 Inhibition of TGF-beta1 signaling abrogated PEPD promoter-driven transcriptional activity of KLF6 an

8 of the Xaa-Pro-cleaving M24B aminopeptidases PEPD and XPNPEP1 called CQ31 selectively activates the C

9 dentify SPATS2L, KCTD18, RPL8, HSD17B12, and PEPD of potential importance in controlling fat cell num

10 w-up of candidate genes, RPL8, HSD17B12, and PEPD were identified as displaying effects on cell proli

11 enotype with characteristics of both IEM and PEPD and show that this mutation renders DRG and trigemi

12 These observations indicate that IEM and PEPD mutants are part of a physiological continuum that

13 ges in channel function seen in both IEM and PEPD mutations: A1632E hyperpolarizes (-7 mV) the voltag

14 patient with overlapping symptoms of IEM and PEPD was reported, displaying a shift of both activation

15 al phenotype with characteristics of IEM and PEPD, with an alanine 1632 substitution by glutamate (A1

16 ynthesized as a transmembrane precursor, but PEPD binding to EGFR can be blocked by EGF.

17 disruption of the fast-inactivated state by PEPD mutations can be more moderate than previously indi

18 In conclusion, PEPD is a ligand of EGFR and presents a novel mechanism

19 (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction < 0.05).

20 Here, we show that peptidase D (PEPD) binds and suppresses over half of nuclear and cyto

21 known as Xaa-Pro dipeptidase or peptidase D (PEPD), is a ubiquitously expressed cytosolic enzyme that

22 Paroxysmal extreme pain disorder (PEPD) and inherited erythromelalgia (IEM) are inherited

23 ted that a paroxysmal extreme pain disorder (PEPD) mutation in the human peripheral neuronal sodium c

24 syndrome, paroxysmal extreme pain disorder (PEPD), characterized by rectal, periocular, and perimand

25 (IEM) and paroxysmal extreme pain disorder (PEPD), enhance Nav1.7 function via distinct mechanisms.

26 Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, OM

27 (IEM) and paroxysmal extreme pain disorder (PEPD).

28 (IEM) and paroxysmal extreme pain disorder (PEPD).

29 neuropathy paroxysmal extreme pain disorder (PEPD).

30 nherited "paroxysmal extreme pain disorder" (PEPD) differs in its clinical picture and affects proxim

31 tudies on CQ31 to develop the optimized dual PEPD/XPNPEP1 inhibitor CQ80 that more effectively induce

32 al and pro-proliferation activities of EGFR, PEPD stimulates DNA synthesis.

33 Eliminating PEPD causes cell death and tumor regression due to p53 a

34 doxorubicin and H2O2 each must free p53 from PEPD in order to achieve robust p53 activation, which is

35 Twelve genes, PPARG, IRS-1, FST, PEPD, PDGFC, MAP3K1, GRB14, ARL15, ANKRD55, RSPO3, COBLL

36 Our work points to novel roles for FST, PEPD, and PDGFC in adipose tissue, with consequences for

37 pression of the candidate causal genes (FST, PEPD, and PDGFC) in the Simpson-Golabi-Behmel syndrome p

38 on levels of these genes (IRS-1, GRB14, FST, PEPD, and PDGFC) in human subcutaneous adipose tissue co

39 rioritized PPARG, IRS-1, GRB14, MAP3K1, FST, PEPD, and PDGFC as top candidate genes.

40 However, PEPD mutations in the S4-S5 linker of domain 3 (D3/S4-S5

41 nt non-PEPD mutation (V1300F) and the I1461T PEPD mutation, located in the putative inactivation gate

42 In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow cu

43 ngly, Sp1 inhibition abrogated KLF6-mediated PEPD promoter activity, suggesting that Sp1 is required

44 sequences required for KLF6 and Sp1-mediated PEPD promoter-driven transcription.

45 d their effects on gating to an adjacent non-PEPD mutation (V1300F) and the I1461T PEPD mutation, loc

46 urgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T.

47 c nor dependent on the enzymatic activity of PEPD.

48 We speculated that selective attenuation of PEPD-enhanced resurgent currents might contribute to thi

49 ed to TGF-beta1 resulted in the induction of PEPD transcription and prolidase expression.

50 tant implications for the pathophysiology of PEPD.

51 We further studied the regulation of PEPD by KLF6 and Sp1 during transforming growth factor b

52 se, but this also renders cells dependent on PEPD for survival, as it suppresses p53.

53 whether a mutation in Nav1.7 leads to IEM or PEPD.

54 Prolidase (PEPD) is the only hydrolase that cleaves the dipeptides

55 inhibits the M24B aminopeptidases prolidase (PEPD) and Xaa-Pro aminopeptidase 1 (XPNPEP1), leading to

56 e viral IFN-I antagonist, NS5, to prolidase (PEPD), a cellular dipeptidase implicated in primary immu

57 nctionally characterized two of the D3/S4-S5 PEPD mutations (V1298F and V1299F) and compared their ef

58 leavage of procaspase-9 at the cleavage site PEPD(315) to yield the large (p35) and small (p12) caspa

59 present in the extracellular space, but that PEPD is released from injured cells and tissues and that

60 n this article, however, we demonstrate that PEPD directly binds to and activates epidermal growth fa

61 We further show that PEPD activates EGFR only when it is present in the extra

62 93 cells expressing wild-type Nav1.7 and the PEPD mutants T1464I and M1627K, we examined the effects

63 By cloning the PEPD promoter into a luciferase reporter and through sit

64 However, the PEPD-p53 complex is critical for p53 response to stress,

65 tisystem disorder caused by mutations in the PEPD gene, which encodes a ubiquitously expressed metall

66 KLF6) and Specificity protein 1 (Sp1) in the PEPD promoter and demonstrate that KLF6/Sp1 transcriptio

67 results identify functional elements of the PEPD promoter for KLF6 and Sp1-mediated transcriptional

68 ported direct binding of KLF6 and Sp1 to the PEPD promoter and this binding was enriched by TGF-beta1

69 In addition to the PEPD site, caspase-9 contains a caspase-3 cleavage site

70 We observed a similar effect with the PEPD mutation I1461T.

71 Interestingly, while all three PEPD mutations increased persistent currents, the relati

72 Thus, PEPD stores p53 for the stress response, but this also r

73 s is a characteristic normally attributed to PEPD-causing mutations.

74 t with biophysical characteristics common to PEPD (impaired fast inactivation) and IEM (hyperpolarize

75 steady-state fast inactivation often lead to PEPD.

76 nce activation, whereas mutations leading to PEPD alter fast inactivation.

77 ing in persistent inward currents similar to PEPD mutations.

78 .7 function due to mutations associated with PEPD, but not IEM, are important in I(NaR) generation, s

79 Furthermore, pain associated with PEPD, but not IEM, is alleviated by the sodium channel i

80 Mutations associated with PEPD, but not IEM, result in destabilized inactivation o

81 haracteristics more commonly associated with PEPD.

82 ty and pain hypersensitivity associated with PEPD.

83 NaR) may play a role in pain associated with PEPD.