ライフサイエンスコーパス: BRCA1 protein

1 d the exon 11-deleted isoforms of the murine Brca1 protein.

2 ongly associated with an ability to modulate BRCA1 protein.

3 xpression, localization, and function of the BRCA1 protein.

4 2 controls the intracellular localization of BRCA1 protein.

5 gnificance lead to amino acid changes in the BRCA1 protein.

6 EZH2 knockdown upregulated BRCA1 protein.

7 RCA1 siRNA, thus silencing the expression of BRCA1 protein.

8 minant negative inhibitor of the full-length BRCA1 protein.

9 onserved and rapidly evolving regions in the BRCA1 protein.

10 transcription factor NF-kappaB, binds to the BRCA1 protein.

11 he RING finger domain of the 1863 amino acid BRCA1 protein.

12 37 breast cancer cells, which contain mutant BRCA1 protein.

13 e due to lack/decreased levels of functional BRCA1 proteins.

14 overexpression of EZH2 and downregulation of BRCA1 proteins.

15 equired for the tumor suppressor function of BRCA1 proteins.

16 olated centrosomes now provide evidence that BRCA1 protein, a suppressor of tumorigenesis in breast a

17 pithelial cells results in nuclear export of BRCA1 protein, aberrant mitoses with extra centrosomes,

18 cancer, but the exact mechanism by which the BRCA1 protein acts to prevent cancer onset remains uncle

19 lation and focus formation of ATM, NBS1, and BRCA1 proteins after IR, they exhibit a defective S-phas

20 These truncated BRCA1 proteins also blocked the ability of ectopically e

21 DNA damage-induced foci (DDI) that contained BRCA1 protein and phosphorylated histone H2AX.

22 gs reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogest

23 nding is localized to amino acids 304-394 of BRCA1 protein and requires the ABC domain of pRb.

24 ssion of p53 resulted in a rapid decrease in BRCA1 protein and RNA levels and BRCA1 promoter-driven l

25 In addition, the induction of BRCA1 protein and transcriptional activation of a BRCA1

26 esence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b prote

27 transcriptional coactivator function for the BRCA1 protein, and more recently, BRCA1 has been implica

28 SKOV-3 CDDP/R, we found increased levels of BRCA1 protein, and we determined that the SKOV-3 CDDP/R

29 ithin the amino- and carboxyl-termini of the BRCA1 protein are required for the inhibition.

30 , these results indicate that RING-deficient BRCA1 proteins are hypomorphic and capable of contributi

31 on; this then forges an association with the BRCA1 protein at sites of DNA damage.

32 The N-terminus of the BRCA1 protein bears a RING finger domain that functions

33 The BRCA1 protein becomes phosphorylated in response to DNA

34 s work we demonstrate that recombinant human Brca1 protein binds strongly to DNA, an activity conferr

35 lls resistant to DNA damage; while truncated BRCA1 proteins blocked the wtBRCA1-induced chemoresistan

36 A specific domain of BRCA1 protein, BRCA1 fragment no. 3 (BF3; amino acids 50

37 We have also characterized two new variant BRCA1 proteins (BRCA1a/p110 and BRCA1b/ p100) which are

38 d not affect the expression of the truncated BRCA1 protein, but caused a loss of transcriptional acti

39 express low or undetectable basal levels of BRCA1 protein, but not in cells with high basal expressi

40 Our findings suggest that truncated BRCA1 proteins can inhibit the function of wild-type BRC

41 itated DNA end resection in the absence of a BRCA1 protein capable of binding CtIP.

42 t the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key co

43 We further found that the BRCA1 protein complexes with the hypophosphorylated form

44 ticular, several carboxyl-terminal truncated BRCA1 proteins conferred chemoresistance, decreased susc

45 nse mutations, is positively correlated with BRCA1 protein conservation.

46 Furthermore, several truncated BRCA1 proteins containing the amino-terminal ER-alpha bi

47 colleagues report a novel mechanism by which BRCA1 protein degradation in response to DNA double-stra

48 om normal thymocytes and found two different BRCA1 proteins, derived from translation of the first an

49 After gamma-irradiation of MCF7 cells, BRCA1 protein dispersed from nucleoli and nucleoplasmic

50 The BRCA1 protein displays E3 ubiquitin ligase activity, and

51 thermore the subcellular localization of the BRCA1 protein does not change throughout the cell cycle.

52 The antibody recognizes a specific BRCA1 protein doublet of about 220 kD.

53 ven amino acids as compared to human, bovine BRCA1 protein exhibited a similar cell cycle-regulated n

54 BRCA1 promoter hypermethylation demonstrated BRCA1 protein expression by immunohistochemistry.

55 Thus, BRCA1 protein expression can be regulated at the transla

56 We used immunohistochemistry to evaluate BRCA1 protein expression in archival tumor samples from

57 Being BRCA1 protein expression strictly linked to the DNA repa

58 Furthermore, Rdd-BRCA1 protein expression was detected in recurrent carci

59 CT domain mutations, have readily detectable BRCA1 protein expression, and are able to proliferate in

60 rotein co-localizes in nuclear foci with the BRCA1 protein following DNA damage and during S-phase, r

61 the N-terminal protein sequence of purified BRCA1 protein from normal thymocytes and found two diffe

62 xic stress, resulting in the displacement of BRCA1 protein from the BRCA1 promoter and subsequent upr

63 Fractionation studies demonstrated that BRCA1 proteins from all species tested interacted specif

64 on with RNA pol II is a conserved feature of BRCA1 proteins from several species.

65 es, and their implications for understanding Brca1 protein function in the context of DNA repair, tum

66 suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p3

67 In this study, purified GAL4-BRCA1 protein functions in transcriptional activation as

68 ce presented here indicates that full-length BRCA1 protein generated by in vitro translation interact

69 The BRCA1 protein has been implicated in the DNA damage resp

70 However, the function of the BRCA1 protein has remained elusive.

71 death, while overexpressing miR-182 reduces BRCA1 protein, impairs homologous recombination-mediated

72 the possibility that the mislocation of the BRCA1 protein in breast cancer cells may be due to a def

73 ited also the HRG-induced down-regulation of BRCA1 protein in breast cancer cells.

74 BRCA1) missense mutations on the function of BRCA1 protein in DNA recombination have been little stud

75 is finding may reflect a direct role for the BRCA1 protein in double strand break (DSB) repair and in

76 investigation, immunohistological studies of BRCA1 protein in frozen breast cancer tissue and MCF7 an

77 ed the expression of p21WAF1/CIP1 and of the BRCA1 protein in MDA-MB-453 cells.

78 n this study, we investigate the role of the BRCA1 protein in modulating a 6-TG-induced MMR damage re

79 ls were deficient in their ability to reduce BRCA1 protein in response to DNA damage, whereas the wil

80 The expression of BRCA1 protein in the BRCA1 transfectants were analysed b

81 ochemically confirmed restored expression of BRCA1 protein in two cases with secondary mutations.

82 BRCA1 protein includes an amino-terminal zinc finger mot

83 The stabilized mutant BRCA1 protein interacted with PALB2-BRCA2-RAD51, was ess

84 ementary systematic screens in search of new BRCA1 protein-interacting partners.

85 Previously, we showed that the BRCA1 protein interacts directly and functionally with e

86 sphorylations, cytoplasmic relocalization of BRCA1 protein is a mechanism whereby BRCA1 function is r

87 ent with this hypothesis, we showed that the BRCA1 protein is absent in 29% of human ULMS and that BR

88 In addition, reduced BRCA1 protein is associated with sporadic cancer cases i

89 ependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER u

90 ts in multiple mouse tissues, and that human BRCA1 protein is expressed and stabilized following expo

91 BRCA1 protein is hyperphosphorylated following various D

92 BRCA1 protein is involved in apoptosis and growth/tumor

93 The BRCA1 protein is known to participate in multiple cellul

94 Because the BRCA1 protein is known to regulate estrogen signaling, w

95 The majority of BRCA1 protein is localized to the nuclear fraction of un

96 It is clear that one of the roles of the Brca1 protein is to facilitate cellular responses to DNA

97 requires fully functional BRCA1 as a mutant BRCA1 protein is unable to localize to the FOXC1 promote

98 l domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module tha

99 be functionally important because a mutated Brca1 protein lacking two phosphorylation sites failed t

100 Loss of functional BRCA1 protein leads to defects in DNA double-strand brea

101 le-regulated protein and tumors with reduced BRCA1 protein level may share molecular features of BRCA

102 to be a growth suppressor gene, no change in BRCA1 protein level was found when MCF10A cells were arr

103 ncreased BRCA1 K11-ubiquitination, decreased BRCA1 protein level, and increased cellular sensitivity

104 Overexpression of SCF(FBXO44) reduces BRCA1 protein level.

105 XO44 as an important protein that influences BRCA1 protein level.

106 , whereas the wild-type counterparts reduced BRCA1 protein levels after exposure to adriamycin.

107 Antagonizing miR-182 enhances BRCA1 protein levels and protects them from IR-induced c

108 mino-17-demethoxygeldanamycin reduced mutant BRCA1 protein levels and restored their sensitivity to P

109 us recombination, probably by regulating the BRCA1 protein levels and the generation of single strand

110 KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination th

111 n and secretion we hypothesized that altered BRCA1 protein levels in breast tumors could affect hypox

112 Accordingly, BRCA1 protein levels were enhanced by silencing of eithe

113 no changes were detected in CstF, BARD1, and BRCA1 protein levels, increased amounts of a CstF/BARD1/

114 In addition to heat regulation of BRCA1 protein levels, we also found that BRCA1 could mod

115 is sufficient for the increase in Rad51 and BRCA1 protein levels.

116 Adriamycin also induced decreases in BRCA1 protein levels; but these decreases required sever

117 estrogen-stimulated MCF7 cells demonstrated BRCA1 protein localization in the granular components of

118 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells tha

119 We found that the expression of the BRCA1 protein may also be regulated at the translational

120 ional variants located within regions of the BRCA1 protein necessary for its tumor suppression activi

121 lls containing reduced amounts of endogenous BRCA1 protein (obtained by transfecting with BRCA1 siRNA

122 dominant-negative effects of putative mutant BRCA1 proteins over wild-type proteins.

123 Evidence suggests that BRCA1 protein plays a key role in mediating DNA damage-i

124 ild-type allele and the cancer cells express Brca1 protein, precluding the chromosomal mechanism for

125 lly interesting gene (RING) domain-deficient BRCA1 protein (Rdd-BRCA1).

126 breast and ovarian cancer cells, most of the BRCA1 protein redistributed to the nucleus revealing a n

127 This surprising phenotype suggests that the BRCA1 protein regulates two functions in the control of

128 Here we show that the steady-state levels of BRCA1 protein remain elevated throughout mitosis but beg

129 sy regarding the subcellular localization of BRCA1 proteins, reports of which have ranged from exclus

130 Small interfering RNA-mediated knockdown of BRCA1 protein resulted in decreased immunofluorescence s

131 or maintaining the low steady-state level of BRCA1 protein seen in many cancer cells.

132 Here, we identify that BRCA1 protein stability is controlled through ubiquitin

133 However, regulation of BRCA1 protein stability is not fully understood.

134 linked ubiquitination pathway that regulates BRCA1 protein stability, dysregulation of which predicts

135 spectrometry to identify Skp1 that regulates BRCA1 protein stability.

136 of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at approximately 1 h after the

137 Why the BRCA1 protein suppresses tumor development specifically

138 due to a deficiency of the cells, wild-type BRCA1 protein tagged with the flag epitope was ectopical

139 insight into the structural features of the BRCA1 protein that are important for its function.

140 cifically recognize an approximately 220-kDa BRCA1 protein that is predominantly expressed in the nuc

141 alternative start codon to generate a novel BRCA1 protein that lacks the first 17 amino acids (Delta

142 interesting new gene domain-less (RING-less) BRCA1 protein that mediated resistance to HRD-targeted t

143 Mutant BRCA1 protein that was inactive as a ubiquitin ligase di

144 ing BRCA1 variants M18T and I42V resulted in BRCA1 proteins that caused centrosome amplification.

145 In studies using epitope-tagged truncated BRCA1 proteins, the ability to stimulate the HSP27 promo

146 ntial mechanism for the nuclear transport of BRCA1 protein, three regions of highly charged, basic re

147 proteasome, calpain, and cathepsins, caused BRCA1 protein to accumulate in the nucleus of several hu

148 egion blocked the ability of the full-length BRCA1 protein to inhibit ER-alpha activity.

149 ors p300 and CBP modulate the ability of the BRCA1 protein to inhibit ER-alpha signaling.

150 istent with the reported localization of the BRCA1 protein to the nucleus, a cytoplasmic localization

151 at lack or impaired binding of the disrupted BRCA1 proteins to E2F, cyclins/CDKs in patients with mut

152 cated (aa 1-100) and full-length (aa 1-1863) BRCA1 proteins to interact with and/or repress ER-alpha

153 We also observed binding of BRCA1 proteins to other ETS-domain transcription factors

154 BRCA1 protein-truncating variants were associated with w

155 diated stabilization of a BRCT domain mutant BRCA1 protein under PARP inhibitor selection pressure.

156 We found that full-length BRCA1 proteins universally fail to activate transcriptio

157 The inhibition of expression of endogenous BRCA1 protein was detected in NIH3T3 transfectants by We

158 The BRCA1 protein was found to associate with ER-alpha in vi

159 Ai to knockdown expression of the endogenous BRCA1 protein, we assessed the level of repression depen

160 ximately 300 residues at both termini of the BRCA1 protein were essential for HDR.

161 BRCA1 proteins were found to be localized mainly in the

162 s, raised against three regions of the human BRCA1 protein, were characterized and revealed BRCA1 as

163 BRCA1 that restored the reading frame of the BRCA1 protein, whereas none of the three platinum-sensit

164 BRCA1 protein, which is involved in DNA damage response,

165 plication forks and surround FANCD2, ATR and BRCA1 proteins, which are located at stalled forks(7,8).

166 Association of the BRCA1 protein with the DNA repair protein Rad51 and chan

167 Physical associations of BRCA1 protein with transcription factors Oct-1 and NF-YA

168 Delta9,10 transcripts predicted to encode a BRCA1 protein with tumor suppression function.We confirm