ライフサイエンスコーパス: hamartin

1 its ubiquitination and for stabilization of hamartin.

2 phosphorylation and reduced interaction with hamartin.

3 y ubiquitinated, and was unable to stabilize hamartin.

4 attenuates the phosphorylation of exogenous hamartin.

5 S6K pathway due to loss of the Tsc1 protein, hamartin.

6 n, vimentin, and desmin are not able to bind hamartin.

7 es reveal that Tuberin, when associated with Hamartin, acts as a Rheb GTPase-activating protein.

8 Plk1 interacts with the N-terminus of hamartin (amino acids 1-880), which contains two potenti

9 Hamartin (amino acids 302-430) and tuberin (amino acids

10 A region of hamartin (amino acids 719-998) predicted to encode coile

11 reveal a novel subcellular localization for hamartin and a novel interaction partner for the hamarti

12 r the hamartin/tuberin complex and implicate hamartin and mTOR in the regulation of centrosome duplic

13 ed to the centrosome and that phosphorylated hamartin and phosphorylated tuberin co-immunoprecipitate

14 esize that the cell proliferative effects of hamartin and tuberin are partly mediated through beta-ca

15 Hamartin and tuberin are products of the tumor suppresso

16 Third, hamartin and tuberin blocked the ability of amino acids

17 Indeed, hamartin and tuberin co-immunoprecipitated with glycogen

18 In cultured cortical neurons, hamartin and tuberin co-localize with neurofilament ligh

19 To address these issues a series of hamartin and tuberin constructs were used to assay for i

20 Hamartin and tuberin form a heterodimer that functions a

21 Hamartin and tuberin form a heterodimer that inhibits th

22 The gene products hamartin and tuberin form the TSC complex that acts as G

23 tenin but not by Disheveled, suggesting that hamartin and tuberin function at the level of the beta-c

24 Here, we show that hamartin and tuberin function together to inhibit mammal

25 vide further genetic evidence for individual hamartin and tuberin functions that may explain some of

26 Indeed, hamartin and tuberin have been shown to interact stably

27 Our data suggest that hamartin and tuberin negatively regulate beta-catenin st

28 ain development as downstream effects of the hamartin and tuberin pathway in TSC.

29 First, coexpression of hamartin and tuberin repressed phosphorylation of 4E-BP1

30 usative genes, TSC1 and TSC2, which code for hamartin and tuberin respectively, play central roles in

31 However, the regions of hamartin and tuberin that interact have not been well de

32 ity of S6K1 was repressed by coexpression of hamartin and tuberin, but the activity of rapamycin-resi

33 Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes

34 Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor

35 BDNF treatment rapidly reduced levels of hamartin and tuberin, negative regulators of mTOR, in a

36 TSC1 and TSC2 (also known as hamartin and tuberin, respectively) form a functional co

37 The proteins encoded by TSC1 and TSC2, hamartin and tuberin, respectively, associate with each

38 Their protein products, hamartin and tuberin, respectively, form a functional co

39 ene products of TSC1 and TSC2, also known as hamartin and tuberin, respectively, form a physical and

40 The TSC1 and TSC2 proteins, also called hamartin and tuberin, respectively, have been shown to r

41 The products of the TSC1 and TSC2 genes, hamartin and tuberin, respectively, heterodimerize and i

42 ions in the TSC1 or TSC2 genes, which encode hamartin and tuberin, respectively.

43 suppressor genes TSC1 or TSC2, which encode hamartin and tuberin, respectively.

44 suppressor genes, TSC1 and TSC2, that encode hamartin and tuberin, respectively.

45 SC2 genes, which encode the protein products hamartin and tuberin, respectively.

46 Hamartin and tuberin, the products of the TSC1 and TSC2

47 Hamartin and tuberin, the products of TSC1 and TSC2, res

48 eport, we demonstrate an interaction between hamartin and tuberin, which is detectable at endogenous

49 in critical growth suppressing functions of hamartin and tuberin.

50 Ectopic expression of hamartin and wild-type tuberin, but not mutant tuberin,

51 from its membrane-bound activation partner (hamartin) and its target GTPase (Rheb) to relieve the gr

52 tuberous sclerosis complex (TSC) genes TSC1 (hamartin) and/or TSC2 (tuberin).

53 ng and dendritic protein synthesis via PTEN, hamartin, and tuberin degradation.

54 t sufficient to mediate the interaction with hamartin, as more N-terminal residues were also required

55 hat cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (Thr417) is in the

56 sites (T417, S584 and T1047) does not impact hamartin binding to Plk1.

57 Here we show that hamartin binds the neurofilament light chain and it is p

58 This allele binds hamartin but has a deletion in the C terminus of tuberin

59 We show that hamartin colocalizes with hypophosphorylated tuberin at

60 and every interacting partner of the tuberin-hamartin complex could potentially alter the disease pre

61 ed as an interactor of Myc, with the tuberin-hamartin complex in the brain.

62 n and proteasomal degradation of the tuberin-hamartin complex particularly in the CNS.

63 the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mTOR signaling

64 mTOR, and increased assembly of the tuberin-hamartin complex.

65 This new murine model of hamartin deficiency exhibits a more severe phenotype tha

66 Hamartin (encoded by TSC1) and S6K was expressed in all

67 Suppression of hamartin expression with TSC1 shRNA viral vectors both i

68 Tuberin and hamartin form a complex that inhibits signaling by the m

69 Tuberin and Hamartin form a tumor suppressor heterodimer that inhibi

70 Tuberin and hamartin function together as a complex in mammals and D

71 e show that at endogenous expression levels, hamartin has a punctate pattern of immunofluorescence in

72 , predicted to encode a novel protein termed hamartin, has recently been cloned from 9q34.

73 Overexpression of the Tuberin-Hamartin heterodimer inhibits Rheb-mediated S6K1 activat

74 Here we show that tuberin-hamartin heterodimers block protein kinase C (PKC)/MAPK-

75 l neurons, Pam co-localizes with tuberin and hamartin in neurites and growth cones.

76 Taken together, the presence of hamartin in the membrane/particulate fraction and its pa

77 Overexpression of hamartin increased resistance to OGD by inducing product

78 Tuberin and hamartin inhibit signaling by the mammalian target of ra

79 ng partner hamartin, suggesting that tuberin-hamartin interactions negatively impact the ability of t

80 Phosphorylated hamartin interacts with Plk1 independent of tuberin with

81 We conclude that hamartin is a growth inhibitory protein whose biological

82 embly of the mTOR regulatory complex Tuberin.Hamartin is disrupted in L6 myoblasts following small in

83 ression of tuberin inhibits cell growth, and hamartin is known to bind tuberin, these results suggest

84 Here, we report that hamartin is localized to the centrosome and that phospho

85 Hamartin is localized to the membrane/particulate (P100)

86 al tuberin, indicating that the stability of hamartin is not dependent on its interaction with tuberi

87 ile the fraction of tuberin that is bound to hamartin is not ubiquitinated.

88 Previously, we have shown that hamartin is phosphorylated by CDC2/cyclin B1 during the

89 Hamartin is present in a cell line derived from the Eker

90 Here, we demonstrate that endogenous hamartin is threonine-phosphorylated during nocodazole-i

91 he tuberous sclerosis complex 1 gene (TSC1), hamartin, is selectively induced by ischemia in hippocam

92 rlie tuberous sclerosis complex, tuberin and hamartin, lie at the center of an important signal trans

93 These results demonstrate that hamartin may anchor neuronal intermediate filaments to t

94 ct with Plk1, whereas a non-phosphorylatable hamartin mutant at residue S332 in conjunction with alan

95 A non-phosphorylatable hamartin mutant with an alanine substitution at residue

96 cated within the putative binding regions of hamartin (N198_F199delinsI;593-595delACT) or tuberin (G2

97 Hamartin negatively regulates the protein levels of Plk1

98 elic inactivation of either TSC genes (TSC1, hamartin or TSC2, tuberin), an event that is implicated

99 ygosity of either TSC1 or TSC2, which encode Hamartin or Tuberin, respectively.

100 y heterozygous mutations in either the TSC1 (hamartin) or the TSC2 (tuberin) gene.

101 ss of function of the tumor suppressor TSC1 (hamartin) or TSC2 (tuberin) and increased angiogenesis,

102 gous mutations in either of two genes, TSC1 (hamartin) or TSC2 (tuberin), are responsible for most ca

103 ated with mutations in TSC1, which codes for hamartin, or TSC2, which codes for tuberin.

104 ingly, in the distal part of the growth cone hamartin overlaps with the ezrin-radixin-moesin family o

105 athway in response to growth factors and how hamartin participates in this process.

106 support a model in which phosphorylation of hamartin regulates the function of the hamartin-tuberin

107 erodimer with the TSC1 gene product TSC1, or hamartin, resulting in a reduction in phosphorylation, a

108 the tuberous sclerosis-1 (TSC1) gene product hamartin results in the inhibition of growth, as well as

109 o bind tuberin, these results suggested that hamartin stabilizes tuberin and this contributes to the

110 's predominant intracellular binding partner hamartin, suggesting that tuberin-hamartin interactions

111 The function of hamartin, the product of TSC1, is not known.

112 Hamartin, the protein product of TSC1, was found to inte

113 In addition, the p70S6K inhibitor hamartin transduced into cells as active protein, interf

114 ing expression of the tuberin (TSC2(-/-)) or hamartin (TSC1(-/-)) genes, consistent with the known ne

115 olipoma showed positive immunoreactivity for hamartin (TSC1) and loss of immunoreactivity for tuberin

116 in either TSC1 or TSC2, whose gene products hamartin (TSC1) and tuberin (TSC2) constitute a putative

117 Phosphorylation of hamartin (TSC1) by CDK1 also negatively regulates the ac

118 We report here that hamartin (TSC1) localizes to the basal body of the prima

119 nt disorder caused by loss or malfunction of hamartin (tsc1) or tuberin (tsc2).

120 on of hamartin regulates the function of the hamartin-tuberin complex during the G2/M phase of the ce

121 However, the regulation of the hamartin-tuberin complex in the context of the physiolog

122 ight chain and it is possible to recover the hamartin-tuberin complex over the neurofilament light ch

123 ritical for some of the CNS functions of the hamartin-tuberin complex, and abolishing this through mu

124 reased the inhibition of p70S6 kinase by the hamartin-tuberin complex.

125 her demonstrate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of

126 tion of tuberin and increased degradation of hamartin-tuberin complexes.

127 by PI3K/Akt is a major mechanism controlling hamartin-tuberin function.

128 three sites, one of which (Thr417) is in the hamartin-tuberin interaction domain.

129 nd -4EBP1 expression in GCs reflects loss of hamartin-tuberin-mediated mTOR pathway inhibition.

130 rtin and a novel interaction partner for the hamartin/tuberin complex and implicate hamartin and mTOR

131 lso negatively regulates the activity of the hamartin/tuberin complex.

132 hese findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mTO

133 In CA1 neurons, hamartin was unaffected by ischemia but was upregulated

134 Co-expression of tuberin stabilized hamartin, which is weakly ubiquitinated, in transiently

135 Hamartin with alanine mutations in the three cyclin-depe

136 ns, and we have validated the interaction of hamartin with moesin.

137 Interaction of hamartin with tuberin forms a heterodimer that inhibits