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 Variants in the Rho domain of
hamartin and the TSC1 binding domain of tuberin preferen
15 esize that the cell proliferative effects of
hamartin and tuberin are partly mediated through beta-ca
16 Hamartin and tuberin are products of the tumor suppresso
17 Third,
hamartin and tuberin blocked the ability of amino acids
18 Indeed,
hamartin and tuberin co-immunoprecipitated with glycogen
19 In cultured cortical neurons,
hamartin and tuberin co-localize with neurofilament ligh
20 To address these issues a series of
hamartin and tuberin constructs were used to assay for i
21 Hamartin and tuberin form a heterodimer that functions a
22 Hamartin and tuberin form a heterodimer that inhibits th
23 The gene products
hamartin and tuberin form the TSC complex that acts as G
24 tenin but not by Disheveled, suggesting that
hamartin and tuberin function at the level of the beta-c
25 Here, we show that
hamartin and tuberin function together to inhibit mammal
26 vide further genetic evidence for individual
hamartin and tuberin functions that may explain some of
27 Indeed,
hamartin and tuberin have been shown to interact stably
28 Our data suggest that
hamartin and tuberin negatively regulate beta-catenin st
29 ain development as downstream effects of the
hamartin and tuberin pathway in TSC.
30 First, coexpression of
hamartin and tuberin repressed phosphorylation of 4E-BP1
31 usative genes, TSC1 and TSC2, which code for
hamartin and tuberin respectively, play central roles in
32 However, the regions of
hamartin and tuberin that interact have not been well de
33 ity of S6K1 was repressed by coexpression of
hamartin and tuberin, but the activity of rapamycin-resi
34 Critical functions of
hamartin and tuberin, encoded by the TSC1 and TSC2 genes
35 Normal cellular functions of
hamartin and tuberin, encoded by the TSC1 and TSC2 tumor
36 BDNF treatment rapidly reduced levels of
hamartin and tuberin, negative regulators of mTOR, in a
37 TSC1 and TSC2 (also known as
hamartin and tuberin, respectively) form a functional co
38 The proteins encoded by TSC1 and TSC2,
hamartin and tuberin, respectively, associate with each
39 Their protein products,
hamartin and tuberin, respectively, form a functional co
40 ene products of TSC1 and TSC2, also known as
hamartin and tuberin, respectively, form a physical and
41 The TSC1 and TSC2 proteins, also called
hamartin and tuberin, respectively, have been shown to r
42 The products of the TSC1 and TSC2 genes,
hamartin and tuberin, respectively, heterodimerize and i
43 mor suppressor gene - TSC1 or TSC2, encoding
hamartin and tuberin, respectively.
44 ions in the TSC1 or TSC2 genes, which encode
hamartin and tuberin, respectively.
45 suppressor genes TSC1 or TSC2, which encode
hamartin and tuberin, respectively.
46 suppressor genes, TSC1 and TSC2, that encode
hamartin and tuberin, respectively.
47 SC2 genes, which encode the protein products
hamartin and tuberin, respectively.
48 Hamartin and tuberin, the products of the TSC1 and TSC2
49 Hamartin and tuberin, the products of TSC1 and TSC2, res
50 eport, we demonstrate an interaction between
hamartin and tuberin, which is detectable at endogenous
51 in critical growth suppressing functions of
hamartin and tuberin.
52 Ectopic expression of
hamartin and wild-type tuberin, but not mutant tuberin,
53 from its membrane-bound activation partner (
hamartin)
and its target GTPase (Rheb) to relieve the gr
54 tuberous sclerosis complex (TSC) genes TSC1 (
hamartin)
and/or TSC2 (tuberin).
55 ng and dendritic protein synthesis via PTEN,
hamartin,
and tuberin degradation.
56 t sufficient to mediate the interaction with
hamartin,
as more N-terminal residues were also required
57 hat cyclin-dependent kinase 1 phosphorylates
hamartin at three sites, one of which (Thr417) is in the
58 sites (T417, S584 and T1047) does not impact
hamartin binding to Plk1.
59 Here we show that
hamartin binds the neurofilament light chain and it is p
60 This allele binds
hamartin but has a deletion in the C terminus of tuberin
61 We show that
hamartin colocalizes with hypophosphorylated tuberin at
62 and every interacting partner of the tuberin-
hamartin complex could potentially alter the disease pre
63 ed as an interactor of Myc, with the tuberin-
hamartin complex in the brain.
64 n and proteasomal degradation of the tuberin-
hamartin complex particularly in the CNS.
65 the tumor suppressor function of the tuberin/
hamartin complex, resulting in increased mTOR signaling
66 mTOR, and increased assembly of the tuberin-
hamartin complex.
67 This new murine model of
hamartin deficiency exhibits a more severe phenotype tha
68 Hamartin (
encoded by TSC1) and S6K was expressed in all
69 Suppression of
hamartin expression with TSC1 shRNA viral vectors both i
70 Tuberin and
hamartin form a complex that inhibits signaling by the m
71 Tuberin and
Hamartin form a tumor suppressor heterodimer that inhibi
72 Tuberin and
hamartin function together as a complex in mammals and D
73 e show that at endogenous expression levels,
hamartin has a punctate pattern of immunofluorescence in
74 , predicted to encode a novel protein termed
hamartin,
has recently been cloned from 9q34.
75 Overexpression of the Tuberin-
Hamartin heterodimer inhibits Rheb-mediated S6K1 activat
76 Here we show that tuberin-
hamartin heterodimers block protein kinase C (PKC)/MAPK-
77 l neurons, Pam co-localizes with tuberin and
hamartin in neurites and growth cones.
78 Taken together, the presence of
hamartin in the membrane/particulate fraction and its pa
79 Overexpression of
hamartin increased resistance to OGD by inducing product
80 Tuberin and
hamartin inhibit signaling by the mammalian target of ra
81 ng partner hamartin, suggesting that tuberin-
hamartin interactions negatively impact the ability of t
82 Phosphorylated
hamartin interacts with Plk1 independent of tuberin with
83 We conclude that
hamartin is a growth inhibitory protein whose biological
84 embly of the mTOR regulatory complex Tuberin.
Hamartin is disrupted in L6 myoblasts following small in
85 ression of tuberin inhibits cell growth, and
hamartin is known to bind tuberin, these results suggest
86 Here, we report that
hamartin is localized to the centrosome and that phospho
87 Hamartin is localized to the membrane/particulate (P100)
88 al tuberin, indicating that the stability of
hamartin is not dependent on its interaction with tuberi
89 ile the fraction of tuberin that is bound to
hamartin is not ubiquitinated.
90 Previously, we have shown that
hamartin is phosphorylated by CDC2/cyclin B1 during the
91 Hamartin is present in a cell line derived from the Eker
92 Here, we demonstrate that endogenous
hamartin is threonine-phosphorylated during nocodazole-i
93 he tuberous sclerosis complex 1 gene (TSC1),
hamartin,
is selectively induced by ischemia in hippocam
94 genetic variants in TSC1 that decrease TSC1/
hamartin levels and predispose to tauopathies such as Al
95 rlie tuberous sclerosis complex, tuberin and
hamartin,
lie at the center of an important signal trans
96 These results demonstrate that
hamartin may anchor neuronal intermediate filaments to t
97 ct with Plk1, whereas a non-phosphorylatable
hamartin mutant at residue S332 in conjunction with alan
98 A non-phosphorylatable
hamartin mutant with an alanine substitution at residue
99 cated within the putative binding regions of
hamartin (
N198_F199delinsI;593-595delACT) or tuberin (G2
100 Hamartin negatively regulates the protein levels of Plk1
101 elic inactivation of either TSC genes (TSC1,
hamartin or TSC2, tuberin), an event that is implicated
102 ygosity of either TSC1 or TSC2, which encode
Hamartin or Tuberin, respectively.
103 y heterozygous mutations in either the TSC1 (
hamartin)
or the TSC2 (tuberin) gene.
104 ss of function of the tumor suppressor TSC1 (
hamartin)
or TSC2 (tuberin) and increased angiogenesis,
105 gous mutations in either of two genes, TSC1 (
hamartin)
or TSC2 (tuberin), are responsible for most ca
106 ated with mutations in TSC1, which codes for
hamartin,
or TSC2, which codes for tuberin.
107 ingly, in the distal part of the growth cone
hamartin overlaps with the ezrin-radixin-moesin family o
108 athway in response to growth factors and how
hamartin participates in this process.
109 support a model in which phosphorylation of
hamartin regulates the function of the hamartin-tuberin
110 erodimer with the TSC1 gene product TSC1, or
hamartin,
resulting in a reduction in phosphorylation, a
111 the tuberous sclerosis-1 (TSC1) gene product
hamartin results in the inhibition of growth, as well as
112 o bind tuberin, these results suggested that
hamartin stabilizes tuberin and this contributes to the
113 's predominant intracellular binding partner
hamartin,
suggesting that tuberin-hamartin interactions
114 The function of
hamartin,
the product of TSC1, is not known.
115 Hamartin,
the protein product of TSC1, was found to inte
116 In addition, the p70S6K inhibitor
hamartin transduced into cells as active protein, interf
117 ing expression of the tuberin (TSC2(-/-)) or
hamartin (
TSC1(-/-)) genes, consistent with the known ne
118 olipoma showed positive immunoreactivity for
hamartin (
TSC1) and loss of immunoreactivity for tuberin
119 in either TSC1 or TSC2, whose gene products
hamartin (
TSC1) and tuberin (TSC2) constitute a putative
120 mour suppressor genes, with encoded proteins
hamartin (
TSC1) and tuberin (TSC2) forming a functional
121 Phosphorylation of
hamartin (
TSC1) by CDK1 also negatively regulates the ac
122 We report here that
hamartin (
TSC1) localizes to the basal body of the prima
123 nt disorder caused by loss or malfunction of
hamartin (
tsc1) or tuberin (tsc2).
124 on of hamartin regulates the function of the
hamartin-
tuberin complex during the G2/M phase of the ce
125 However, the regulation of the
hamartin-
tuberin complex in the context of the physiolog
126 ight chain and it is possible to recover the
hamartin-
tuberin complex over the neurofilament light ch
127 ritical for some of the CNS functions of the
hamartin-
tuberin complex, and abolishing this through mu
128 reased the inhibition of p70S6 kinase by the
hamartin-
tuberin complex.
129 her demonstrate that Akt/PKB associates with
hamartin-
tuberin complexes, promoting phosphorylation of
130 tion of tuberin and increased degradation of
hamartin-
tuberin complexes.
131 by PI3K/Akt is a major mechanism controlling
hamartin-
tuberin function.
132 three sites, one of which (Thr417) is in the
hamartin-
tuberin interaction domain.
133 nd -4EBP1 expression in GCs reflects loss of
hamartin-
tuberin-mediated mTOR pathway inhibition.
134 rtin and a novel interaction partner for the
hamartin/
tuberin complex and implicate hamartin and mTOR
135 lso negatively regulates the activity of the
hamartin/
tuberin complex.
136 hese findings strongly implicate the tuberin-
hamartin tumor suppressor complex as an inhibitor of mTO
137 In CA1 neurons,
hamartin was unaffected by ischemia but was upregulated
138 Co-expression of tuberin stabilized
hamartin,
which is weakly ubiquitinated, in transiently
139 Hamartin with alanine mutations in the three cyclin-depe
140 ns, and we have validated the interaction of
hamartin with moesin.
141 Interaction of
hamartin with tuberin forms a heterodimer that inhibits