ライフサイエンスコーパス: SRC-2

1 mmatory genes by recruiting the coactivator, SRC-2.

2 In addition, SRC-2 ablation, in both a whole-body and liver-specific

3 Modulating SRC-2 action may, thus, represent a novel therapeutic ta

4 our understanding of the mechanism by which SRC-2 acts in normal and stressed hearts and allows furt

5 coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent

6 a decidual response, confirming that uterine SRC-2 and -1 cooperate in P-initiated transcriptional pr

7 In addition, functional analysis of SRC-2 and SRC-3 coactivators indicated that the SRC fami

8 Together, we demonstrate that SRC-2 and SRC-3 concomitantly promote human adipocyte di

9 The related coactivators SRC-2 and SRC-3 interact with peroxisome proliferator ac

10 SRC-2 and SRC-3 knockdown increases the proportion of ce

11 e probed this equilibrium by down-regulating SRC-2 and SRC-3 while simultaneously quantifying PPARgam

12 ymerase II and steroid receptor coactivators SRC-2 and SRC-3, and changes in histone acetylation.

13 upporting dominant, pro-adipogenic roles for SRC-2 and SRC-3, SRC-1 knockdown does not affect adipoge

14 y was fully prevented by cotransfection with SRC-2, and partially prevented with exogenous SRC-1.

15 coactivator (SRC) family, SRC-1, TIF2/GRIP1/SRC-2, and pCIP/ACTR/AIB-1/RAC-3/TRAM-1/SRC-3.

16 SRC-1, SRC-2, and SRC-3 all enhanced IkappaB alpha transcriptio

17 stigated recruitment of coactivators (SRC-1, SRC-2, and SRC-3) and corepressors (HDAC1, HDAC2, HDAC3,

18 rely, steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) represent emerging targets in cancer t

19 ily of steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) steer the functional output of numerou

20 Our results position SRC-2 as a critical regulator of mammalian glucose produ

21 Collectively, these findings position SRC-2 as a major regulator of polygenic inputs to metabo

22 Additionally, we describe SRC-2 as a novel regulator of PPARalpha expression, thus

23 een in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer met

24 e identified the transcriptional coactivator SRC-2 as a regulator of fasting hepatic glucose release,

25 d with mass spectrometry, we have identified SRC-2 as an indispensable integrator of transcriptional

26 tial role of steroid receptor coactivator-2 (SRC-2) as a co-regulator in the transcription of critica

27 ells (PCs) preferentially express SRC-1 over SRC-2, but SRC-2 mRNA is slightly elevated in the SRC-1(

28 duced immediately, suggesting replacement of SRC-2 by SRC-1.

29 We found that SRC-2 CKO mice exhibit markedly decreased left ventricul

30 t that cardiomyocyte-specific loss of SRC-2 (SRC-2 CKO) results in a blunted hypertrophy accompanied

31 lated SRC-2 expression in vitro Furthermore, SRC-2 coactivated the transcription factors GATA-binding

32 d binding domain in complex with LCA and the SRC-2 coactivator peptide reveals the binding of two LCA

33 al regulator steroid receptor coactivator-2 (SRC-2) controls activation of several key cardiac transc

34 These results suggest that SRC-2 coordinates cardiomyocyte secretion of VEGF downst

35 by eliminating potential indirect effects of SRC-2 deletion in other organs.

36 As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we cross

37 tumors identified a massive increase in the SRC-2-driven metabolic signature in metastatic tumors co

38 ulate angiogenesis, both of which stimulated SRC-2 expression in vitro Furthermore, SRC-2 coactivated

39 eologenesis in the hormone-treated PR(Cre/+) SRC-2(flox/flox) mammary gland, reinforcing an important

40 while ovarian activity was normal, PR(Cre/+) SRC-2(flox/flox) mouse uterine function was severely com

41 Moreover, removal of SRC-1 in the PR(Cre/+) SRC-2(flox/flox) mouse uterus resulted in the absence of

42 lyses revealed an inability of the PR(Cre/+) SRC-2(flox/flox) mouse uterus to undergo the necessary c

43 mployed to generate a mouse model (PR(Cre/+) SRC-2(flox/flox)) in which SRC-2 function was abrogated

44 nd the previous information by demonstrating SRC-2 fulfills this role by serving as a critical coacti

45 model (PR(Cre/+) SRC-2(flox/flox)) in which SRC-2 function was abrogated only in cell lineages that

46 ssed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased

47 ary gland, reinforcing an important role for SRC-2 in cellular proliferative changes that require PR.

48 Moreover, deletion of Ncoa2/Src-2 in mice predisposes to diethylnitrosamine-induced

49 d transcriptional intermediary factor (TIF)2/SRC-2 in mouse resulted in distinctive mutant phenotypes

50 Absence of SRC-2 in PR-positive uterine cells was shown to contribu

51 ming correlated with the early expression of SRC-2 in the SRC-1(-)/- PCs.

52 n, but the cardiomyocyte-specific effects of SRC-2 in these changes are unknown.

53 Moreover, the genetic manipulation of SRC-2 in this study is specific for the heart and thereb

54 her support the predicted roles of SRC-1 and SRC-2 in, respectively, PR- and GR-mediated transcriptio

55 Pressure overload in mice lacking SRC-2 induces an abrogated hypertrophic response and dec

56 Moreover, SRC-2 inhibition in murine models severely attenuated th

57 ranscription factor expression and activity, SRC-2 is a critical transcriptional regulator of genes i

58 We conclude that SRC-2 is appropriated by PR in a subset of transcription

59 We have shown that SRC-2 is critical to transcriptional control modulated b

60 t brain structures where SRC-1 is expressed, SRC-2 is expressed at lower levels; however, SRC-3 mRNA

61 SRC-2 is expressed in PCs after postnatal day (P) 10.

62 ID/DeltaID) Src-1(-/-) mice, suggesting that SRC-2 is responsible for T(3) sensitivity in the absence

63 sequences of deletion of SRC-2 on bone using SRC-2 knock out (KO) mice.

64 Of note, SRC-2 knockdown in cardiomyocytes decreased VEGF express

65 SRC-2 KO mice also had a marked decrease (by 50%) in bon

66 wild type mice, marrow stromal cultures from SRC-2 KO mice formed significantly more mineralized nodu

67 SRC-2 resulted in increased bone mass, with SRC-2 KO mice having 80% higher trabecular bone volume a

68 suggested that marrow precursor cells in the SRC-2 KO mice may be resistant to the inhibitory effects

69 rogen replacement, we also demonstrated that SRC-2 KO mice were partially resistant to the skeletal a

70 d that in bone marrow stromal cells, loss of SRC-2 leads to destabilization of the transcription comp

71 tively, these findings indicate that loss of SRC-2 leads to partial skeletal resistance to the ER and

72 l key cardiac transcription factors and that SRC-2 loss results in extensive cardiac transcriptional

73 SRC-2 modulates G6Pase expression directly by acting as

74 preferentially express SRC-1 over SRC-2, but SRC-2 mRNA is slightly elevated in the SRC-1(-)/- PCs.

75 steroid receptor coactivators (SRCs) SRC-1, SRC-2 [nuclear receptor coactivator (NCOA)2], and SRC-3

76 we examined the consequences of deletion of SRC-2 on bone using SRC-2 knock out (KO) mice.

77 PARgamma and lipogenesis, without changes in SRC-2 or SRC-3, we hypothesized that permissive coregula

78 using cells individually depleted of SRC-1, SRC-2, or SRC-3 by small interfering RNA.

79 nstrate that Steroid Receptor Coactivator 2 (SRC-2) orchestrates a hierarchy of nutritionally respons

80 Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for

81 ing hepatic glucose release, a function that SRC-2 performs by controlling the expression of hepatic

82 cts RTH in Src-1(-/-) mice through increased SRC-2 recruitment to T(3) target genes.

83 related coactivator SRC-2, we found enhanced SRC-2 recruitment to TR-binding regions of genes in NCoR

84 oid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet

85 Loss of SRC-2 resulted in increased bone mass, with SRC-2 KO mic

86 t, SRC-1 signal was increased gradually, but SRC-2 signal was reduced immediately, suggesting replace

87 e report that cardiomyocyte-specific loss of SRC-2 (SRC-2 CKO) results in a blunted hypertrophy accom

88 t it requires steroid receptor coactivators (SRC-2, SRC-3) and the mediator component MED14.

89 nalysis to quantify links between PPARgamma, SRC-2, SRC-3, and lipogenesis.

90 In prostate cancer cells, SRC-2 stimulated reductive carboxylation of alpha-ketogl

91 receptor (GR) preferentially associated with SRC-2 (TIF-2/GRIP-1), which subsequently recruited pCAF

92 ator (SRC) family composed of SRC-1 (NCOA1), SRC-2 (TIF2/GRIP1/NCOA2), and SRC-3 (AIB1/ACTR/NCOA3).

93 ctivators, which includes SRC-1 (NCoA-1) and SRC-2 (TIF2/GRIP1/NCoA2).

94 erase II, PR, and the coactivators SRC-1 and SRC-2 to the distal region and basal promoter.

95 tamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then t

96 ors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the meta

97 SRC-2 was highly elevated in a variety of tumors, especi

98 on assays (ChIP) for the related coactivator SRC-2, we found enhanced SRC-2 recruitment to TR-binding

99 receptor coactivator 2 (NCoA2, also known as SRC-2), which is frequently amplified or overexpressed i

100 oid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the part

101 further validate three of these genes, Ncoa2/Src-2, Zfx, and Dtnb, as tumor suppressors in liver canc