ライフサイエンスコーパス: PALA

1 y 5-FU 425 mg/m(2) on days 1 to 5; (cycle 2) PALA 250 mg/m(2) on days 29, 36, 43, and 50 and 5-FU 2,6

2 acid (FA), N-phosphonacetyl-L-aspartic acid (PALA), and recombinant interferon alfa-2a (IFNalpha-2a)

3 Even though p53 is activated, PALA-treated cells expressing low levels of p53 or lacki

4 In addition, PALA treatment inhibited Bcl-2, and overexpression of Bc

5 a superfamily, increases substantially after PALA treatment, and application of exogenous MIC-1 or it

6 The non-genotoxic agents PALA, taxol and nocodazole induced p53 accumulation and

7 Although PALA-induced DNA damage occurs only in dividing cells, t

8 h and, rarely, to cad gene amplification and PALA resistance.

9 atment with N-(phosphonoacetyl)-L-aspartate (PALA) at concentrations that normally lead to arrest in

10 e to the drug N-phosphonoacetyl-L-aspartate (PALA) compared to TGF-beta 1-expressing control keratino

11 treated with N-(phosphonacetyl)-L-aspartate (PALA) continue to synthesize DNA slowly and eventually p

12 d malonate, or N-phosphonacetyl-l-aspartate (PALA) have previously been made in the space group P321,

13 sis inhibitor N-phosphonoacetyl-l-aspartate (PALA) produced a pyrimidine deficit with minimal mortali

14 trate analogue N-phosphonacetyl-L-aspartate (PALA) required to activate the mutant enzyme to the same

15 esistance to N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of the synthesis of pyrimidine nucle

16 metabolite, N-(phosphonoacetyl)-L-aspartate (PALA), is defective, whereas p53 induction and G1 arrest

17 te analogue N-(phosphonoacetyl)-l-aspartate (PALA), or the aspartate analogue succinate, in the prese

18 e moiety of N-(phosphonoacetyl)-l-aspartate (PALA), the carboxylates of Asp interact with the same re

19 lase inhibitor N-phosphonacetyl-l-aspartate (PALA), which blocks the synthesis of pyrimidine nucleoti

20 tent inhibitor N-phosphonacetyl-l-aspartate (PALA), which combines the binding features of Asp and CP

21 treated with N-(phosphonacetyl)-L-aspartate (PALA), which inhibits pyrimidine nucleotide synthesis, l

22 response to N-(phosphonacetyl)-L-aspartate (PALA), which starves them for pyrimidine nucleotides, an

23 esis inhibitor N-phosphonacetyl-L-aspartate (PALA), which, in addition to selecting for cells contain

24 formation of N-(phosphoacetyl)-L-aspartate (PALA)-resistant (PALA(R)) colonies, mediated by gene amp

25 he presence of N-phosphonacetyl-L-aspartate (PALA).

26 bstrate analog N-phosphonacetyl-L-aspartate (PALA).

27 rate analog, N-(phosphonacetyl)-L-aspartate (PALA).

28 eatment with N-(phosphonacetyl)-l-aspartate (PALA).

29 uggest distinct pathways of p53 induction by PALA and ionizing radiation.

30 hinge closure and other changes promoted by PALA binding to the holoenzyme are stabilized by ligand

31 manner by which the Q137A enzyme coordinates PALA, especially in the side-chain positions of Arg105 a

32 hat two distinct events are required to form PALA-resistant REF52 cells: amplification of cad, whose

33 remarkable protection of p53-null cells from PALA-mediated apoptosis, arguing that the p53-dependent

34 on of p53 in these cells protected them from PALA-induced apoptosis by activating p21, sustaining the

35 p53-deficient HT1080 cells generated PALA-resistant variants containing amplified CAD genes a

36 (UV, IR, and adriamycin) and non-genotoxic (PALA, taxol, nocodazole) stress in cultured human cells

37 However, these cells still fail to give PALA-resistant colonies and are protected from DNA damag

38 However, PALA treatment inhibited the expression of DeltaNp73 onl

39 ation) produced a dose-dependent increase in PALA(R) colonies, and combining expression of mutant p53

40 produced a greater than additive increase in PALA(R) colony formation.

41 odes of the six crystallographic independent PALA molecules are virtually identical to one another, a

42 rexpression of Bcl-2 significantly inhibited PALA-induced apoptosis.

43 presence of either subsaturating amounts of PALA or succinate and carbamoyl phosphate) caused a hype

44 ngs increased the frequency of appearance of PALA(R) colonies after subsequent exposure to PALA.

45 teric C trimer resulting from the binding of PALA, we determined the 1.95-A resolution crystal struct

46 rmolecular contacts influence the binding of PALA.

47 idues that interact with the carboxylates of PALA, although the position and orientations are shifted

48 posure to a high, selective concentration of PALA, promotes the formation of PALA-resistant cells in

49 t of REF52 cells with a low concentration of PALA, which slows DNA replication but does not trigger c

50 The anomalous effect of PALA suggests that, in the coupled reaction, the effecti

51 entration of PALA, promotes the formation of PALA-resistant cells in which the physically linked cad

52 mplification and the consequent formation of PALA-resistant colonies.

53 reminiscent of the reported modification of PALA-bound R-state by Mg-ATP.

54 structure was determined in the presence of PALA to 2.7 angstroms resolution.

55 37A and wild-type enzymes in the presence of PALA were identical.

56 might help to revitalize the clinical use of PALA, which has been limited by gut toxicity.

57 the binding of Asp in the presence of CP or PALA, these inhibitors are unable to initiate the global

58 In the complete absence of p53, PALA-treated cells continue to synthesize DNA slowly and

59 sion of endogenous N-myc in these pretreated PALA-resistant cells allows them to bypass the p53-media

60 phosphoacetyl)-L-aspartate (PALA)-resistant (PALA(R)) colonies, mediated by gene amplification.

61 icantly inhibited apoptosis, suggesting that PALA-induced apoptosis was mediated via TAp73-dependent

62 The PALA assay is designed to measure directly the frequency

63 inactive, taut (T state) holoenzyme and the PALA complex are attributable to localized effects of in

64 ely resembles the liganded C subunits in the PALA-bound holoenzyme.

65 In contrast to the control lines, the PALA-mediated G1 arrest did not occur in the TGF-beta 1

66 ession of N-myc, whose product overcomes the PALA-induced cell cycle block.

67 As further test, the PALA, a bisubstrate analogue, was displaced by citrate a

68 In contrast to the free C trimer, the PALA-bound trimer exhibits approximate threefold symmetr

69 We have used the PALA assay to analyse the effects of the human T-cell le

70 ALA(R) colonies after subsequent exposure to PALA.

71 of the CAD gene, which confers resistance to PALA.

72 estigated apoptotic signaling in response to PALA and the role of p53 expression in this pathway.

73 t the ability to arrest in G1 in response to PALA.

74 resolution crystal structure of the C trimer-PALA complex.

75 The C trimer-PALA structure closely resembles the liganded C subunits

76 the ability of cells to undergo the typical PALA-mediated G(1) phase cell cycle arrest, thereby allo

77 Conformational changes in the C trimer upon PALA binding include ordering of two active site loops a

78 e R-state structure of wild-type enzyme with PALA bound.

79 und that treatment of cells lacking p53 with PALA induced TAp73, Noxa and Bim and inactivation of the

80 rosarcoma cell line HT1080 when treated with PALA or with methotrexate, an antifolate that, under the