ライフサイエンスコーパス: mortalin

1 P1) regulation, suggesting a unique role for mortalin.

2 ation in a complex with the chaperon protein mortalin.

3 gen-responsive genes SOX5, RBM15, Dynein and Mortalin.

4 At 6 hours, the RNA level for mortalin-2, a pro-survival gene, was upregulated.

5 RT-PCR was performed for 18s, mortalin-2, cathepsins B, D, and L/V2.

6 ed and duplicated centrosomes, we identified mortalin, a member of heat shock protein family, as a pr

7 0-fold above normal clam hemocytes) of human mortalin, an Hsp70 family protein.

8 mmunoprecipitation we have demonstrated that mortalin and p53 proteins are complexed in the cytoplasm

9 tor of mortalin, disrupts the interaction of mortalin and p53 proteins, resulting in translocation of

10 cation requires physical interaction between mortalin and p53.

11 200b, miR-200c, and miR-217 as regulators of mortalin and, perhaps indirectly, of CD46 and CD55.

12 ion in MEK/ERK-activated cancer and identify mortalin as a molecular switch that mediates the tumor-s

13 C cell survival and proliferation, proposing mortalin as a novel therapeutic target for MTC.

14 etion and HIV-1 virus release, we identified mortalin as an SMR-specific cellular protein.

15 Thus, our present findings not only identify mortalin as an upstream molecule of p53 but also provide

16 in human and other animal cancers displaying mortalin-based cytoplasmic sequestration of the p53 tumo

17 these topoisomerase II poisons may result as mortalin-based cytoplasmic tethering is overwhelmed by d

18 odels for human cancers displaying a similar mortalin-based phenotype.

19 In addition, mortalin can potentially target the C8 and C9 complement

20 In this study, we demonstrated that mortalin can regulate MEK/ERK activity via protein phosp

21 trates that p21(CIP1) has dual effects under mortalin-depleted conditions, i.e., mediating cell cycle

22 Nevertheless, mortalin depletion did not affect cellular PP1alpha leve

23 Moreover, mortalin depletion downregulated RET expression independ

24 fferent MEK/ERK-activated cancer cell lines, mortalin depletion induced cell death and growth arrest,

25 Intriguingly, mortalin depletion induced growth arrest partly via the

26 nisms underlying these effects revealed that mortalin depletion induces transient MEK/ERK (extracellu

27 markably, MEK/ERK activity was necessary for mortalin depletion to induce p21(CIP1) expression in B-R

28 ocytes with MKT-077, a cationic inhibitor of mortalin, disrupts the interaction of mortalin and p53 p

29 t suppression of centrosome duplication, and mortalin-driven centrosome duplication requires physical

30 pacity against CDC relative to mitochondrial mortalin-EGFP.

31 Following transfection, mortalin-enhanced GFP (EGFP) is located primarily in mit

32 on and in vitro binding assays revealed that mortalin facilitates PP1alpha-mediated MEK1/2 dephosphor

33 ily chaperones could not effectively replace mortalin for p21(CIP1) regulation, suggesting a unique r

34 One interactor was mortalin/GRP75, a homolog of the yeast ssq1 chaperone th

35 Mortalin/GRP75, the mitochondrial heat shock protein 70,

36 rocess involving the mitochondrial chaperone mortalin/GRP75.

37 We found that mortalin (HSPA9/GRP75), a member of HSP70 family, is upr

38 Here we report that mortalin (HSPA9/GRP75/PBP74) is a novel negative regulat

39 We previously reported that mortalin/HSPA9 can facilitate proliferation of certain K

40 ation, suggesting a nonconventional role for mortalin in promoting PP1alpha-MEK1/2 interaction.

41 on between C5b-9 deposition and the level of mortalin in the cell.

42 body inhibition we demonstrated that the Nef/mortalin interaction is necessary for exNef secretion.

43 eriments with full-length Nef confirmed that mortalin interacts with Nef via Nef's SMR motif and that

44 These data demonstrate that mortalin is a key regulator of multiple signaling and me

45 We found that mortalin is present in the MEK1/MEK2 proteome and is upr

46 emia cells to CDC, whereas overexpression of mortalin leads to their resistance to CDC.

47 Further analysis revealed that mortalin localized to centrosomes in late G1 before cent

48 strated that, to compensate for reduction in mortalin mRNA level, the cells increased the rate of syn

49 for miR-200b, miR-200c, or miR-217 enhanced mortalin mRNA level.

50 miR-217 regulatory sites were identified in mortalin mRNA.

51 -200b/c or miR-217 lowered the expression of mortalin mRNA.

52 express its full protective effect from CDC, mortalin must first reach the mitochondria.

53 cell types exhibiting normal MEK/ERK status, mortalin overexpression suppressed B-Raf(V600E)- or Delt

54 Overexpression of mortalin overrides the p53-dependent suppression of cent

55 lites or the mitochondrial chaperone mtHsp75/mortalin partially reverses the inflammation-associated

56 Moreover, mortalin promotes dissociation of p53 from centrosomes t

57 rrelation between exNef secretion levels and mortalin protein expression.

58 iRNA modulators had no significant effect on mortalin protein level.

59 the cells increased the rate of synthesis of mortalin protein.

60 n leukemic clam hemocytes, wild-type p53 and mortalin proteins co-localize in the cytoplasm.

61 nced its release from the cells and promoted mortalin relocation to the plasma membrane.

62 p53 mutant that lacks the ability to bind to mortalin remains at centrosomes, and suppresses centroso

63 Overexpression and microRNA knockdown of mortalin revealed a positive correlation between exNef s

64 As shown here, interference with mortalin synthesis enhances sensitivity of K562 erythrol

65 Similar to intact mortalin, the ATPase domain, but not the substrate-bindi

66 Two functional domains of mortalin, the N-terminal ATPase domain and the C-termina

67 Binding of mortalin to complement C9 and C8 occurs through an ionic

68 cancer biopsy specimens in correlation with mortalin upregulation.

69 Mortalin was previously shown by us to bind to component

70 rate-binding cavity and the substrate lid of mortalin were necessary for these physical interactions,

71 cancers p53 is tethered in the cytoplasm by mortalin when the latter protein is overexpressed.

72 have a role in tumorigenesis in concert with mortalin, which affects MEK/ERK activity in tumor cells.