ライフサイエンスコーパス: SASP

1 SASP is a program that can be induced by oncogenes or DN

2 However, some cells can develop a SASP comprising factors that are immunosuppressive and p

3 izing radiation or oncogenic RAS developed a SASP regardless of whether they expressed p16(INK4a).

4 vein endothelial cells (HUVECs) developed a SASP that could be suppressed by targeting the JAK pathw

5 NK4a)-positive cells may not always harbor a SASP in vivo and, furthermore, that the SASP is not a co

6 p21(CIP1/WAF1), induces senescence without a SASP, even though they induced other features of senesce

7 as(V12)-transformed NIH 3T3 cells, activated SASP gene expression, and recruited the CBP coactivator

8 etylase (HDAC) inhibitors robustly activated SASP in the absence of DNA breaks, suggesting that DDR-d

9 form (P41) was assayed for activity against SASP and the zymogen form (P46) was assayed for the abil

10 Variants inactive against SASP and unable to autoprocess were analyzed by circular

11 8MAPK activation was sufficient to induce an SASP, and p53 restrained p38MAPK activation.

12 In SASP-A and SASP-C of Bacillus megaterium two conserved glutamate re

13 The structure of both DNA and SASP alters upon their association and this causes major

14 mation was associated with decreased OIS and SASP and a protumorigenic tumor microenvironment that ha

15 s biliary constituents affect senescence and SASP in cultured human cholangiocytes.

16 nt reduction in cholangiocyte senescence and SASP is a new therapeutic approach for PSC.

17 anscription factor GATA4 as a senescence and SASP regulator.

18 e show that mice with reduced senescence and SASP responses exhibit decreased tumour-inducing potenti

19 ogated experimentally induced senescence and SASP.

20 sms involved in cholangiocyte senescence and SASP.

21 in bile induced cholangiocyte senescence and SASP.

22 d share a common signature of senescence and SASP.

23 , we consider the evidence for the SASP and "SASP-like" inflammation in driving skin carcinogenesis,

24 hese genes cause the loss of the appropriate SASP from spores, and the sspK, sspM and sspO (and likel

25 or tlp loci cause a loss of the appropriate SASP from spores, but have no discernible effect on spor

26 e that senescence and a stem cell-associated SASP drive cell transformation and tumour initiation in

27 Loss of HMGB2 during senescence blunts SASP gene expression by allowing for spreading of repres

28 s from a negative feedback loop activated by SASP-mediated endoplasmic reticulum (ER) stress.

29 We found that expression of the canonical SASP members interleukin (IL)-6 and IL-8, but not OPN, w

30 amined the molecular mechanisms that control SASP activation, focusing on the known SASP factor osteo

31 Here, we delineate another crucial SASP regulatory pathway and its relationship to the DDR

32 ely 1 h at 70 degrees C), and the deamidated SASP no longer bound to DNA effectively.

33 of DNA breaks, suggesting that DDR-dependent SASP activation occurs in response to chromatin remodeli

34 plication and DDR activation, thus disabling SASP expression.

35 n of the small, acid-soluble protein family (SASP) from spore samples on the MALDI sample holder.

36 The removal of macroH2A1 from SASP genes results from a negative feedback loop activat

37 f ATM, which mediates removal macroH2A1 from SASP genes.

38 ation during OIS, including its removal from SASP gene chromatin.

39 consistent with the absence of a functional SASP.

40 How SASP genes are excluded from SAHF-mediated global gene s

41 In SASP-A and SASP-C of Bacillus megaterium two conserved g

42 ayed in spore outgrowth and more impaired in SASP degradation than were spores from a gpr single muta

43 eading us to investigate the role of MLL1 in SASP expression.

44 hese findings assign p38MAPK a novel role in SASP regulation--one that is necessary, sufficient, and

45 spreading of repressive heterochromatin into SASP gene loci.

46 ntrol SASP activation, focusing on the known SASP factor osteopontin (OPN).

47 teins (SASP), but the DPA-less spores lacked SASP-gamma.

48 of the positive feedback loop that maintains SASP gene expression and triggers the induction of parac

49 racts from spores which lack the three major SASP (alpha, beta, and gamma).

50 ition markedly reduced the secretion of most SASP factors, constitutive p38MAPK activation was suffic

51 pe, alpha/beta-type SASP but not by a mutant SASP that binds DNA poorly.

52 Notably, SASP sensitized breast cancer cells to inhibitors of the

53 r pro-inflammatory factors including a novel SASP component CLEC11A.

54 The specificity of the observed SASP peptides was evaluated using a cross-species sequen

55 hromatin spreading to allow for exclusion of SASP gene loci from a global heterochromatin environment

56 lpha expression and restricted expression of SASP components IL-6 and IL-8.

57 This correlates with incorporation of SASP gene loci into SAHF.

58 GB2) orchestrates the chromatin landscape of SASP gene loci.

59 vel activity of simvastatin and mechanism of SASP regulation.

60 standing of both the roles and mechanisms of SASP expression may offer new targets for skin cancer pr

61 critical control point for the regulation of SASP gene expression during senescence.

62 scence and suppresses basal transcription of SASP genes.

63 however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore,

64 enescence-associated secretory phenotype, or SASP), and reduced expression of the nuclear lamina prot

65 s a novel master regulator that orchestrates SASP through prevention of heterochromatin spreading to

66 a senescence-associated secretory phenotype (SASP) characterized by IL1B, CXCL8, CCL2, TNF, CCL27 and

67 , p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6).

68 e senescence-associated secretory phenotype (SASP) gene transcription signature.

69 f senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires

70 d senescence-associated secretory phenotype (SASP) in livers of patients with PSC, primary biliary ci

71 n senescence-associated secretory phenotype (SASP) in particular have revealed various layers of func

72 e senescence-associated secretory phenotype (SASP) in systemic aging, sirtuin family regulation of me

73 s senescence-associated secretory phenotype (SASP) includes various factors that are synthesized as t

74 a senescence-associated secretory phenotype (SASP) involving the production of factors that reinforce

75 e senescence-associated secretory phenotype (SASP) is a hallmark of senescence with an important phys

76 e senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue.

77 e senescence-associated secretory phenotype (SASP) that attenuates acinar-to-ductal metaplasia, pancr

78 a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointer

79 e senescence-associated secretory phenotype (SASP) that contribute to tumor suppression by enforcing

80 a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammat

81 e senescence-associated secretory phenotype (SASP), a pro-inflammatory response linked to tumor promo

82 he senescent-associated secretory phenotype (SASP), and over expression of H2A.J increases the expres

83 s senescence-associated secretory phenotype (SASP), dominated by IL-6.

84 e senescence-associated secretory phenotype (SASP), senescent cells can paradoxically promote carcino

85 a senescence-associated secretory phenotype (SASP), the function of which is unclear.

86 a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tum

87 e senescence-associated secretory phenotype (SASP), which can reinforce the arrest and induce senesce

88 e senescence-associated secretory phenotype (SASP), which helps to maintain the senescent state and t

89 e senescence-associated secretory phenotype (SASP), which itself favors reprogramming.

90 , senescence-associated secretory phenotype (SASP)-mediated tissue damage, and involvement in adipose

91 e senescence-associated secretory phenotype (SASP).

92 a senescence-associated secretory phenotype (SASP).

93 e senescence-associated secretory phenotype (SASP).

94 e senescence-associated secretory phenotype (SASP).

95 a senescence-associated secretory phenotype (SASP).

96 e senescence-associated secretory phenotype (SASP).

97 e senescence-associated secretory phenotype (SASP).

98 e senescence-associated secretory phenotype (SASP).

99 e senescence-associated secretory phenotype (SASP).

100 e senescence-associated secretory phenotype (SASP).

101 y senescence-associated secretory phenotype (SASP).

102 e senescence-associated secretory phenotype (SASP).

103 eam regulator of the SA secretory phenotype (SASP).

104 nditions; expression of profibroinflammatory SASP components (i.e., IL-6, IL-8, CCL2, PAI-1) was also

105 eta-type, small, acid-soluble spore protein (SASP) from Bacillus subtilis, was generated that has a v

106 beta-type small, acid-soluble spore protein (SASP) of Bacillus subtilis took place readily in vitro (

107 beta-type small, acid-soluble spore protein (SASP) SspC(wt) were designed to evaluate the contributio

108 protease's small acid-soluble spore protein (SASP) substrates, SASP-gamma.

109 ith a group of small, acid-soluble proteins (SASP) that protect DNA from a variety of harsh treatment

110 encoding minor small, acid-soluble proteins (SASP) unique to spores of Bacillus subtilis are expresse

111 ing new, minor small, acid-soluble proteins (SASP) unique to spores of Bacillus subtilis are expresse

112 Eleven small, acid-soluble proteins (SASP) which are present in spores but not in growing cel

113 lpha/beta-type small, acid-soluble proteins (SASP), colocalized to these nucleoid rings early in spor

114 lpha/beta-type small, acid-soluble proteins (SASP), that protect the spore's DNA against different ty

115 lpha/beta-type, small acid-soluble proteins (SASP), which are the major chromosomal proteins in spore

116 lpha/beta-type small, acid-soluble proteins (SASP).

117 e core known as small acid-soluble proteins (SASP).

118 eta-type small, acid-soluble spore proteins (SASP) are essential for the resistance of DNA in spores

119 mma-Type small, acid-soluble spore proteins (SASP) are the most abundant proteins in spores of at lea

120 ation of small, acid-soluble spore proteins (SASP) during germination of spores of Bacillus and Clost

121 beta-type small acid-soluble spore proteins (SASP) is the major determinant of DNA resistance to dama

122 eta-type small, acid-soluble spore proteins (SASP) of Bacillus species were readily oxidized to methi

123 Small, acid-soluble spore proteins (SASP) of the alpha/beta-type from several Bacillus speci

124 eta-type small, acid-soluble spore proteins (SASP) that are synthesized in the developing forespore a

125 eta-type small, acid-soluble spore proteins (SASP) to DNA of spores of Bacillus species is the major

126 beta-type small acid-soluble spore proteins (SASP), but the DPA-less spores lacked SASP-gamma.

127 group of small, acid-soluble spore proteins (SASP), which are synthesized in the developing spore and

128 More broadly, MLL1 inhibition also reduces "SASP-like" inflammatory gene expression from cancer cell

129 cid-soluble spore protein (SASP) substrates, SASP-gamma.

130 h the pharmacologic inhibitor sulfasalazine (SASP).

131 We speculate that SASP inhibition by JAK inhibitors may contribute to alle

132 The SASP is proposed to underlie age-related pathologies, in

133 omas, and low expression of both RB1 and the SASP genes was associated with poor prognosis.

134 Therefore, senescent cells and the SASP represent significant opportunities for advancement

135 ible contribution of senescent cells and the SASP to age-related inflammation and frailty.

136 s based on targeting senescent cells and the SASP, and potential paths to developing clinical interve

137 he mechanisms that induce senescence and the SASP, their associations with chronic disease and frailt

138 a DNA binding protein and is cleaved by the SASP-specific protease (GPR) at a site similar to that c

139 Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protei

140 his review, we consider the evidence for the SASP and "SASP-like" inflammation in driving skin carcin

141 covers a primary and beneficial role for the SASP in promoting cell plasticity and tissue regeneratio

142 se findings define a beneficial role for the SASP in tissue repair and help to explain why the SASP e

143 a complex and often conflicting role for the SASP in tumorigenesis and treatment response.

144 ng is essential, but not sufficient, for the SASP, which is restrained by p53.

145 ndergoing senescence and is required for the SASP.

146 However, the SASP has also been shown to favor embryonic development,

147 Mechanistically, p38MAPK induced the SASP largely by increasing NF-kappaB transcriptional act

148 anscription factor NF-kappaB to initiate the SASP and facilitate senescence.

149 Likewise, the SASP in treated cancers can either contribute to durable

150 pression closely correlated with that of the SASP cassette in human osteosarcomas, and low expression

151 activation promotes OIS via elevation of the SASP factor CXCL1 (also known as KC), which activates CX

152 Here we uncover timely new functions of the SASP in promoting a proregenerative response through the

153 tory phenotype through the regulation of the SASP initiator IL-1alpha, creating a microenvironment pe

154 and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation.

155 Despite the importance of the SASP to tumor biology, it is virtually unknown how trans

156 of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on

157 NF-kappaB acts as a master regulator of the SASP, influencing the expression of more genes than RB a

158 ss is known about pathways that regulate the SASP.

159 Further, p38MAPK regulated the SASP independently of the canonical DDR.

160 irect role for p16(INK4a) in suppressing the SASP.

161 or a SASP in vivo and, furthermore, that the SASP is not a consequence of p16(INK4a) activation or se

162 However, prolonged exposure to the SASP causes a subsequent cell-intrinsic senescence arres

163 use keratinocytes transiently exposed to the SASP exhibit increased expression of stem cell markers a

164 in tissue repair and help to explain why the SASP evolved.

165 related pathologies and inflammation through SASP secretion.

166 ifespan in vivo, potentially in part through SASP reduction.

167 g endospore-forming bacteria, contributes to SASP degradation but that its function is normally maske

168 HMGB2 preferentially localizes to SASP gene loci during senescence.

169 escribe how chromatin-bound HMGB2 fine tunes SASP expression by avoiding heterochromatin spreading.

170 es lacking one or both major alpha/beta-type SASP (alpha- and alpha- beta- strains, respectively).

171 s or in spores lacking major alpha/beta-type SASP (alpha- beta- spores) had no effect on sporulation

172 genome, including two minor alpha/beta-type SASP (SspC and SspD) and a putative spore coat protein (

173 wo methionine residues of an alpha/beta-type SASP (SspC) in spores of Bacillus subtilis, although one

174 In the complex, the alpha/beta-type SASP adopt a helix-turn-helix motif, interact with DNA t

175 y, but DNA binding protected alpha/beta-type SASP against methionine oxidation by peroxides in vitro.

176 ubtilis spores lacking major alpha/beta-type SASP and overexpressing SspC(DeltaN11-D13K-C3) had a 10-

177 of the spores' pool of major alpha/beta-type SASP and was delayed when alpha/beta-type SASP degradati

178 However, alpha/beta-type SASP are even more strongly protected against deamidatio

179 re at 2.1 A resolution of an alpha/beta-type SASP bound to a 10-bp DNA duplex.

180 of either of two wild-type, alpha/beta-type SASP but not by a mutant SASP that binds DNA poorly.

181 y be important in vivo since alpha/beta-type SASP containing oxidized methionine residues no longer b

182 here it is bound to DNA, the alpha/beta-type SASP deamidated with a t(1/2) of 2 to 3 h at 95 degrees

183 omplex and the physiology of alpha/beta-type SASP degradation during spore germination are discussed.

184 pe SASP and was delayed when alpha/beta-type SASP degradation was delayed.

185 ts rapid degradation of this alpha/beta-type SASP early in germination.

186 In all four alpha/beta-type SASP examined, the amino donor in the EDC induced amide

187 P, variants of SspC (a minor alpha/beta-type SASP from Bacillus subtilis) with modified N termini wer

188 te the interchangeability of alpha/beta-type SASP in DNA protection in spores.

189 ing with oxidative damage to alpha/beta-type SASP in spores is DNA binding, which protects the protei

190 synthesize both DPA and most alpha/beta-type SASP in strain PS3664 (sspA sspB sleB spoVF) resulted in

191 A mutant alpha/beta-type SASP in which the reactive asparagine was changed to asp

192 Folding of alpha/beta-type SASP induced by a variety of DNAs and oligonucleotides w

193 The primary sequence of alpha/beta-type SASP is highly conserved; however, the N-terminal third

194 These results indicate that alpha/beta-type SASP may well have global effects on gene expression dur

195 These oxidized alpha/beta-type SASP no longer bound to DNA effectively, but DNA binding

196 pores, HBsu colocalized with alpha/beta-type SASP on the nucleoid, suggesting that HBsu could modulat

197 in modulating the effects of alpha/beta-type SASP on the properties of DNA in the developing and dorm

198 Thus, not only do alpha/beta-type SASP protect spore DNA from damage; DNA also protects al

199 ular details of both DNA and alpha/beta-type SASP protection in the complex and thus also in spores.

200 ies showed that HBsu altered alpha/beta-type SASP protection of pUC19 from DNase digestion, induced n

201 of a model for DNA-dependent alpha/beta-type SASP protein-protein interaction involving the N-termina

202 Analysis of several alpha/beta-type SASP showed that these proteins have essentially no seco

203 moderately strong binding of alpha/beta-type SASP to DNA is important to balance the potentially conf

204 However, the alpha/beta-type SASP was extremely resistant to deamidation within spore

205 which is highly conserved in alpha/beta-type SASP was only oxidized to a small degree.

206 h several of the DNA-binding alpha/beta-type SASP were present.

207 Incubation of an oxidized alpha/beta-type SASP with peptidyl methionine sulfoxide reductase (MsrA)

208 to methionine, restored the alpha/beta-type SASP's ability to bind to DNA.

209 resistance on spores lacking alpha/beta-type SASP, and spores with SspC(Delta11-D13K) triggered germi

210 ndicate that, in addition to alpha/beta-type SASP, DPA also is extremely important in spore resistanc

211 An alpha/beta-type SASP, Ssp2, from Clostridium perfringens was expressed a

212 is of the interaction of one alpha/beta-type SASP, SspC(Tyr), with DNA indicated that each binding ev

213 ifferences between different alpha/beta-type SASP, the N-terminal regions of these proteins are invol

214 in the N-terminal region of alpha/beta-type SASP, variants of SspC (a minor alpha/beta-type SASP fro

215 no longer bind DNA well and alpha/beta-type SASP-DNA binding is essential for long-term spore surviv

216 vity factors (omega), as the alpha/beta-type SASP-DNA interaction was significantly cooperative, with

217 um binding parameters of the alpha/beta-type SASP-DNA interaction.

218 ificantly interfere with the alpha/beta-type SASP-mediated changes in the UV photochemistry of DNA th

219 and greatly ameliorated the alpha/beta-type SASP-mediated increase in DNA persistence length.

220 ve DNA supercoiling opposing alpha/beta-type SASP-mediated positive supercoiling, and greatly amelior

221 ing that HBsu could modulate alpha/beta-type SASP-mediated properties of spore DNA.

222 spores with lower levels of alpha/beta-type SASP.

223 ynthesis of normal levels of alpha/beta-type SASP.

224 om damage; DNA also protects alpha/beta-type SASP.

225 acking the majority of their alpha/beta-type SASP.

226 e similar to that cleaved in alpha/beta-type SASP.

227 ngs for the structure of the alpha/beta-type SASP.DNA complex and the physiology of alpha/beta-type S

228 A gamma-type SASP of B. subtilis also deamidated readily in vitro (t(

229 Current work has shown that the gamma-type SASP or their coding genes (sspE genes) are present in m

230 In addition, no gamma-type SASP were found in A. acidocaldarius spores, although se

231 termining the precise function of gamma-type SASP.