ライフサイエンスコーパス: MCL1

1 MCL1 (ML1 myeloid cell leukemia 1), a Bcl-2 (B- cell lym

2 MCL1 has effects similar to those of BCL2, up-regulation

3 MCL1 is a member of the BCL2 family that is highly regul

4 MCL1 is a viability-promoting member of the BCL2 family

5 MCL1 is essential for the survival of stem and progenito

6 MCL1 pathway alterations were found in 22% of cases and

7 MCL1 thus sets the stage for the development of lymphoma

8 MCL1 was defined as a target for downregulation by miR-3

9 MCL1, which encodes the antiapoptotic protein MCL1, is a

10 g pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA.

11 o ancestry-specific myeloid cell leukemia 1 (MCL1) expression in B cells and ancestry-specific allele

12 Incubation with the myeloid cell leukemia 1 (MCL1) inhibitor S63845, a proapoptotic BH3-mimetic thera

13 ro-survival protein myeloid cell leukemia 1 (MCL1) is overexpressed in many cancers, but the developm

14 Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulat

15 rget is the protein myeloid cell leukemia 1 (MCL1), a critical prosurvival factor in cancers such as

16 cally, synthesis of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play a role in

17 phosphorylation of myeloid cell leukemia 1 (MCL1), another viability-promoting BCL2 family member.

18 prosurvival protein myeloid cell leukemia-1 (MCL1).

19 tinguishes myeloid cell leukemia sequence 1 (MCL1) from BCL2 dependence in myeloma cell lines.

20 ription of myeloid cell leukemia sequence-1 (MCL1), an antiapoptotic B cell leukemia-2 family member.

21 , BCL2, BCL-XL, and myeloid cell leukemia 1 [MCL1]) remain poorly understood.

22 7 [19%]), MYC (23 [12%]), ARID1A (21 [11%]), MCL1 (19 [10%]), PIK3CA (17 [9%]), ERBB2 (16 [8%]), PTEN

23 d venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after ch

24 tional repressors that preferentially affect MCL1 due to its short mRNA half-life.

25 n the G2/M phase and was not found to affect MCL1 turnover.

26 c drugs despite thrombin exposure, affirming MCL1's functional importance.

27 ction and cell death induction via alternate MCL1 splicing.

28 H3 and H4 of the H3K4 methylated alternative MCL1 exon 2 nucleosome.

29 Mice expressing an MCL1 transgene in hematolymphoid tissues have now been m

30 pendent phosphorylation, which results in an MCL1 band shift and is induced by events in G(2)/M or pr

31 eport shows that transgenic expression of an MCL1 protein enhances survival of memory CD8(+) T cells

32 BCL2 and MCL1 are commonly expressed prosurvival (antiapoptotic)

33 (BCL2L2), BCLb (BCL2L10), BFL1 (BCL2A1) and MCL1 -- also cooperate with MYC to accelerate leukemogen

34 These included the BCL2L1 and MCL1 combination, which was also effective in imatinib-r

35 We query the anti-apoptotic genes BCL2L1 and MCL1, and the DNA damage repair gene PARP1, identifying

36 While BCL2A1, BCL2L2 and MCL1 are prone to splicing perturbation, BCL2L1 exhibits

37 ggest that combination of TKIs with BCL6 and MCL1 inhibitors may potentially lead to the complete era

38 tosis in BCL2A1-dependent melanoma cells and MCL1-dependent NSCLC cells.

39 findings suggest that profiling the FBW7 and MCL1 status of tumours, in terms of protein levels, mess

40 EGR2, which in turn leads to cell growth and MCL1-mediated cell survival.

41 d a close relationship between FBW7 loss and MCL1 overexpression.

42 of two regulators promoting OXPHOS, MYC and MCL1, and effectively alleviates tumor hypoxia.

43 Transcriptional repressors and MCL1 shRNAs induced apoptosis in the same cancer cell li

44 l for sensitivity toward both venetoclax and MCL1 inhibition.

45 examined the expression of BCL2, BCL-XL, and MCL1 in primary human hematopoietic subsets and leukemic

46 f antiapoptotic proteins (BCL-W, BCL-XL, and MCL1) selectively reduced cell viability when combined w

47 optotic factors, including BCL2, BCL-XL, and MCL1.

48 ersus stabilized expression of antiapoptotic MCL1 is thus controlled by N-terminal truncation as well

49 imals revealed lower levels of antiapoptotic MCL1, a higher propensity to apoptosis, and a diminished

50 During mitotic arrest, MCL1 protein levels decline markedly, through a post-tra

51 portunity - strengthening weak links such as MCL1 could result in a delay or complete abrogation of c

52 nificant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly af

53 nd translation of key survival genes such as MCL1.

54 f transcripts with a short half-life such as MCL1.

55 correlated with higher BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios.

56 disruption in the same genes (such as BCL9, MCL1, ARNT (also known as HIF1B), TERT and MYC) within s

57 ed chromosomes 1q21 (which encompasses BCL9, MCL1 and ARNT), 5p15.33 (TERT), 11q13.3 (CCND1), 19q12 (

58 Because MCL1 is a major mechanism of resistance to ABT-737, thes

59 ro and in vivo, modulating BAD-BCLXL and BIM-MCL1 interactions, with durable anti-tumour activity in

60 Low MCL1 expression and high BIM:MCL1 or BIM:BCL2 ratios in leukemic cells correlated wit

61 A mutant of MCL1 that lacks PCNA binding (MCL1(Delta)(4A)) could not inhibit cell cycle progressio

62 USP9X binds MCL1 and removes the Lys 48-linked polyubiquitin chains

63 BCL2-like structural folds belonging to both MCL1 and BAK.

64 ctions to displace BAK from sequestration by MCL1 and BCL-X(L).

65 Here, we characterise MCL1 in multiple mCRPC biopsy cohorts and patient-derive

66 In contrast, MCL1(Delta)(4A) retained its anti-apoptotic function in

67 tion correlated with the level of cyclin D1, MCL1, and phospho-BAD, which also correlated with FGFR-i

68 ved oncoproteins including c-MYC, Cyclin D1, MCL1, and the PIM1/2 kinases themselves.

69 ds, including anthracyclines, that decreased MCL1 expression.

70 SY-1365 treatment decreased MCL1 protein levels, and cancer cells with low BCL2L1 (B

71 5 sensitivity of myeloma cells by decreasing MCL1-BAX complexes.

72 ws turnover of the normally rapidly degraded MCL1 protein; however, okadaic acid and taxol induce ERK

73 modifications may contribute to dysregulated MCL1 expression in cancer and represent targets for prom

74 e rescued by physiological levels of ectopic MCL1 expression.

75 enriched for FBW7 inactivation and elevated MCL1 levels, underscoring the prominent roles of these p

76 ases MCL1 polyubiquitination, which enhances MCL1 turnover and cell killing by the BH3 mimetic ABT-73

77 multiple myeloma survival genes, especially MCL1, TNK2, CDK11, and WBSCR22, exhibited differential e

78 estores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mecha

79 proteins that are constitutively expressed, MCL1 is inducibly expressed in cells that are recently e

80 Overall, expression MCL1 can increase during the induction of cell death as

81 icting navitoclax sensitivity, and extensive MCL1*BAK complexes predicting A1210477 sensitivity.

82 In fact, MCL1, not other Bcl-2 family proteins, contained the PCN

83 ed to a decrease in the antiapoptotic factor MCL1, which is often upregulated in NSCLC.

84 The RR by histology was as follows: MCL1, 38%; MCL2, 37%; IMC, 28%; and SLL, 14%.

85 bility profile given physiological roles for MCL1 in several nonhematologic tissues.

86 mily members can functionally substitute for MCL1, when it is inhibited by S63845.

87 ion ratios changes the requirement away from MCL1 and toward the dominant BCL2 family gene.

88 1 released the proapoptotic protein BAK from MCL1, and Bak deficiency conferred resistance to transcr

89 Furthermore, MCL1 inhibitor but not BCL2 inhibitor combined with NK c

90 vealed that NO66 activates the survival gene MCL1, the invasion-associated genes IGFBP5 and MMP3, the

91 growth and expression of the MYC target gene MCL1.

92 educed expression of the antiapoptotic genes MCL1 and BCLXL.

93 essing expression of the antiapoptotic genes MCL1, XIAP, BCL-xL, SURVIVIN, and MDM2.

94 reased transcription of antiapoptotic genes (MCL1 and BFL1).

95 Interestingly, high MCL1 to BCL-xl messenger RNA determines whether the cell

96 of mouse and human results that explain how MCL1 can block an important negative consequence of MYC

97 cell stimulation, and mice expressing human MCL1 as a transgene exhibited a skewing in the proportio

98 A 162-base pair segment of the human MCL1 5'-flank was found to direct luciferase reporter ac

99 Proliferation of intestinal stem cells in MCL1-deficient mice required WNT signaling and was assoc

100 nhibitor PD 98059) prevented the increase in MCL1 expression and caused rapid cell death by apoptosis

101 family was found to precede the increase in MCL1 expression produced by 12-O-tetradecanoylphorbol 13

102 the mechanism of the TPA-induced increase in MCL1 expression seen in myelomonocytic cells at early st

103 To assess whether this increase in MCL1 expression was associated with enhanced protection

104 The DNA damage-induced increase in MCL1 mRNA did not depend upon p53 as it was seen in cell

105 The increase in MCL1 occurred rapidly and was transient, levels of the M

106 activation was necessary for the increase in MCL1, as inhibition of the increase in ERK phosphorylati

107 gen-specific CD8(+) T cells were observed in MCL1 transgenic mice.

108 phosphorylation associated with reduction in MCL1 levels and phosphorylation, illustrating a potent m

109 hibitors is maintained; however, a switch in MCL1 dependence occurs.

110 al EBV super-enhancer (ESE) targets included MCL1, IRF4, and EBF.

111 athways and differently-expressed, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, an

112 resses other anti-apoptotic genes, including MCL1 and BCL2A1.

113 not have this marked effect did not increase MCL1.

114 polysaccharide, okadaic acid) also increased MCL1 expression.

115 d USP9X expression correlates with increased MCL1 protein in human follicular lymphomas and diffuse l

116 Knockdown of USP9X increases MCL1 polyubiquitination, which enhances MCL1 turnover an

117 kadaic acid and taxol induce ERK-independent MCL1 phosphorylation at additional discrete sites.

118 nt (BAX) and others through p53-independent (MCL1) pathways.

119 bule-damaging agents, such as taxol, induced MCL1 phosphorylation associated with a band shift to dec

120 kinase (ERK) activation blocked TPA-induced MCL1 phosphorylation but not the taxol-induced band shif

121 TPA-induced MCL1 phosphorylation occurred rapidly and was not associ

122 and NOXA, which can then bind to and inhibit MCL1.

123 hway through which many BH3 mimetics inhibit MCL1 and suggest the potential use of these agents as ad

124 siRNA-fortilin) did not affect intracellular MCL1 level, the depletion of intracellular MCL1 by siRNA

125 r MCL1 level, the depletion of intracellular MCL1 by siRNA-MCL1 was associated with the significant r

126 hancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR.

127 udies demonstrate that S63845 potently kills MCL1-dependent cancer cells, including multiple myeloma,

128 both N-terminally truncated and full-length MCL1 contain sequences enriched in proline, glutamic aci

129 Fortilin, like MCL1, was rapidly inducible in serum-stimulated human ao

130 ssociations were found in nine genetic loci (MCL1-ENSA, GCKR, AGR3-AHR, ADH1B, ALDH1B1, ALDH1A1, ALDH

131 Low MCL1 expression and high BIM:MCL1 or BIM:BCL2 ratios in

132 s is stronger in CRC, correlating with a low MCL1:BCL-X(L) ratio; indeed the MCL1:BCL-X(L) ratio is p

133 nked polyubiquitin chains that normally mark MCL1 for proteasomal degradation.

134 compared with ML-1 cells expressing maximal MCL1 on exposure to phorbol-12-myristate-13- acetate.

135 Finally, CDK9-mediated MCL1 downregulation combined with AKT inhibition recapit

136 We identified the Bcl2 family member MCL1 and several 26S proteasome subunits among the most

137 The antiapoptotic BCL2 family member MCL1 is normally up- and down-modulated in response to e

138 sion of the pro-survival BCL-2 family member MCL1, which occurs via inhibition of STAT5A.

139 on expression of another BCL2 family member, MCL1, a gene expressed during ML-1 cell differentiation.

140 Another antiapoptotic family member, MCL1, exhibits a difference in electrophoretic mobility

141 -regulated anti-apoptotic BH3 family members MCL1 and BCL-XL sensitizing PTCL cells to BH3 mimetic dr

142 s exhibit enhanced survival and express more MCL1 and less Bim.

143 Moreover, MCL1 inhibition, either alone or in combination with oth

144 n following ribavirin treatment include MYC, MCL1, NBN, BCL2 and BIRC5.

145 re-sensitization to CDK9 inhibitor, but not MCL1 inhibitor.

146 rt the identification of fortilin as a novel MCL1-interacting protein by screening of a yeast two-hyb

147 2/BCL-xL inhibitor navitoclax, and the novel MCL1 inhibitor AZD5991.

148 Genetic ablation of MCL1 sensitizes TNBC cells to cytotoxic drugs despite th

149 uced apoptosis in response to an ablation of MCL1-L by meayamycin B.

150 s to examine selected membrane activities of MCL1 and BAK under apoptotic-like conditions.

151 OS stress also caused deglutathionylation of MCL1, followed by a rapid degradation of this cell survi

152 The degradation of MCL1 was blocked in patient-derived tumour cells that la

153 hase experiment showed that the depletion of MCL1 by siRNA-MCL1 was associated with the rapid degrada

154 ion strategy for the clinical development of MCL1 inhibitors.

155 ies are covered by the N-terminal domains of MCL1.

156 mage causes an increase in the expression of MCL1 along with increases in GADD45 and BAX and a decrea

157 Expression of MCL1 was found to increase upon exposure of ML-1 cells t

158 The increase in expression of MCL1 was further studied using a panel of human cell lin

159 EGFR signaling stimulates the expression of MCL1, an antiapoptotic protein, and a family of EGR tran

160 vealed that the BCL2-like structural fold of MCL1, but not that of BAK, forms stable heterodimeric co

161 cell survival because the truncated form of MCL1 (unlike those of BCL2 and BCLX) retained antiapopto

162 The N-terminally truncated form of MCL1 was expressed to varying extents in normal lymphoid

163 n, and the cell cycle regulatory function of MCL1 is mediated through its interaction with PCNA.

164 h high affinity to the BH3-binding groove of MCL1.

165 is strategy actually leads to an increase of MCL1 protein levels.

166 Co-inhibition of MCL1 and AKT induces cancer-specific cell death in PTEN-

167 in CML cells, including the long isoform of MCL1, which proved to be essential for the antiapoptotic

168 The level of MCL1 protein was 5-fold elevated compared with ML-1 cell

169 correlated with increased protein levels of MCL1 and BCL2 target genes.

170 ent plasma cells expressed reduced levels of MCL1 relative to wild-type controls, and transgenic expr

171 , however, express abnormally high levels of MCL1, contributing to chemoresistance and disease relaps

172 addition, the intracellular localization of MCL1(Delta)(4A) was identical to that of wild type MCL1.

173 Loss of MCL1 results in development of intestinal carcinomas, ev

174 Loss of MCL1 retained intestinal crypts in a hyperproliferated s

175 The mechanism of MCL1 overexpression in cancer is not well understood.

176 ly increased the electrophoretic mobility of MCL1 and differed from the phosphorylation/band shift to

177 es not alter the electrophoretic mobility of MCL1, and (ii) ERK-independent phosphorylation, which re

178 A mutant of MCL1 that lacks PCNA binding (MCL1(Delta)(4A)) could not

179 on rate, demonstrated that overexpression of MCL1 results in increased mitochondrial respiration and

180 take assay showed that the overexpression of MCL1 significantly inhibited the cell cycle progression

181 hibiting amplification and overexpression of MCL1, indicate that such cells may exhibit increased sen

182 e of the normal, highly regulated pattern of MCL1 expression, in addition to providing a model for st

183 Phosphorylation of MCL1 directs its interaction with the tumour-suppressor

184 The polyubiquitylation of MCL1 then targets it for proteasomal degradation.

185 ch was found quite stable in the presence of MCL1.

186 for halting the antiapoptotic properties of MCL1 revolve around inhibiting its sequestration of proa

187 Furthermore, pulldown of MCL1 by endogenous PTBP1 verifies that these proteins in

188 teraction with the 3' untranslated region of MCL1 mRNA.

189 ary DNA containing only the coding region of MCL1 rescued H23 cells from the toxicity of a 3' untrans

190 t not a siRNA targeting the coding region of MCL1.

191 The up-regulation of MCL1 and EGR2 by EGF was further confirmed in osteoproge

192 Repression of MCL1 released the proapoptotic protein BAK from MCL1, an

193 Our data suggest the roles of MCL1 and ARID1A in BL pathogenesis and demonstrate that

194 be phenocopied by RNAi-mediated silencing of MCL1.

195 1 alternative exon and alter the splicing of MCL1 pre-mRNA.

196 ins were involved in alternative splicing of MCL1.

197 s T-ALL progression through stabilization of MCL1 and suggest that impeding this pathway has potentia

198 otes leukemogenesis by regulating stimuli of MCL1 expression.

199 IF4B results in reduced protein synthesis of MCL1, which, in turn, induces apoptotic cell death of ca

200 Pharmacologic targeting of MCL1 in a mouse model of chronic cholestasis reduces DR-

201 tic deletion of the pro-apoptotic targets of MCL1, Bak and Bax, rescued the survival of NK cells foll

202 edominantly nuclear and identical to that of MCL1, as shown by immunostaining and confocal microscopy

203 tment by supporting efficient translation of MCL1.

204 lax resulted in compensatory upregulation of MCL1, we established a three-drug combination composed o

205 t of tumour cell lines exhibit dependence on MCL1 expression for survival and this dependence is also

206 tients with TCL and functional dependence on MCL1.

207 l cycle control inhibition and dependency on MCL1.

208 ing to select TCL PDX that were dependent on MCL1.

209 ily members, PEL cells are dependent only on MCL1, suggesting that MCL1 may have nonredundant functio

210 ty of BCL-XL-encoding BCL2L1 but not BCL2 or MCL1, for the survival of erythroid/megakaryoblastic leu

211 ty of these molecules for BCL2, BCL-X(L), or MCL1 has been established in vitro; whether they inhibit

212 On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establis

213 noma (HNSCC), up to 90% of which overexpress MCL1 and BCL-X(L).

214 osis at least in part through inhibiting p38-MCL1 pro-survival pathway.

215 hly transcribed target genes like MYC, PIM1, MCL1, CD30, IL2RA, CDC25A and IL4R.

216 6, EFEMP1) gene signature (GS) that predicts MCL1 inhibitor sensitivity in TNBC cells.

217 genes regulate signaling pathways to promote MCL1 inhibitor resistance.

218 was found to have amplified the prosurvival MCL1 gene (3-fold) and overexpressed the MCL1 protein.

219 overexpression of the antiapoptotic protein MCL1 was sufficient to circumvent apoptosis in this sett

220 The antiapoptotic protein MCL1, a member of the BCL2 family, is required for maint

221 d the functions of the antiapoptotic protein MCL1, another member of the BCL2 family, in intestinal h

222 CL1, which encodes the antiapoptotic protein MCL1, is among the most frequently amplified genes in hu

223 ncing stability of the antiapoptotic protein MCL1; therefore, IRAK inhibition reduced MCL1 stability

224 ve downregulation of the prosurvival protein MCL1.

225 Here we show that the pro-survival protein MCL1 is a crucial regulator of apoptosis triggered by an

226 ted with release of the pro-survival protein MCL1.

227 Myeloid cell leukemia 1 protein (MCL1) is an anti-apoptotic protein that is structurally

228 Overexpression of anti-apoptotic proteins MCL1 and Bcl-xL are frequently observed in many cancers.

229 unctions by binding the BCL2 family proteins MCL1 and BFL1.

230 ty, IFNT upregulated cell survival proteins (MCL1, BCL-xL, and XIAP) and reduced the levels of gamma-

231 tic and molecular approach for the recurrent MCL1 amplicon at chromosome 1 in human tumor cells.

232 ein MCL1; therefore, IRAK inhibition reduced MCL1 stability and sensitized T-ALL to combination thera

233 Nuclear factors that regulate MCL1 transcription have now been identified, extending t

234 cin B up-regulated MCL1-S and down-regulated MCL1-L.

235 otting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L.

236 ptional and post-transcriptional regulation, MCL1 is subject to multiple, separate, post-translationa

237 In the acquired resistance setting, MCL1 suppression in response to HSP90 inhibitors is main

238 t showed that the depletion of MCL1 by siRNA-MCL1 was associated with the rapid degradation of fortil

239 the depletion of intracellular MCL1 by siRNA-MCL1 was associated with the significant reduction of th

240 how that the deubiquitinase USP9X stabilizes MCL1 and thereby promotes cell survival.

241 to occur within the 20S proteasome subunits, MCL1, RRM1, USP8, and CKAP5.

242 phocyte count GWASs for variants surrounding MCL1.

243 irectly (MCL1i) or indirectly (CDK9i) target MCL1.

244 ein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylat

245 Inhibitors targeting MCL1 are in clinical development, however numerous cance

246 l molecules capable of selectively targeting MCL1 using a proteolysis targeting chimera (PROTAC) meth

247 ses the level and stability of GSK3 targets, MCL1, NRF2, and particularly SNAIL.

248 eveals the screening accuracy of 85% and TAZ-MCL1 is characterized as combinational drug targets for

249 el is now presented, which demonstrates that MCL1 can undergo distinct phosphorylation events - media

250 ting the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathw

251 gnostic value in this setting, we found that MCL1 overexpression does correlate with poor patient sur

252 emic blasts from AML patients and found that MCL1 transcripts were consistently expressed at high lev

253 from undergoing apoptosis, it is likely that MCL1, an anti-apoptotic protein inducible by growth and

254 These findings show that MCL1 can shape the makeup of the CD8(+) T cell response,

255 reagents and hemocyte monolayers showed that MCL1 functions as an antiadhesive protective coat becaus

256 This is important because it shows that MCL1 expression may be an important determinant of the f

257 in AML pathogenesis in mice and suggest that MCL1 may be a promising therapeutic target in patients w

258 These data suggest that MCL1, in addition to being an anti-apoptotic molecule, s

259 An in vitro pull-down assay suggested that MCL1 is the only Bcl-2 family protein to interact with P

260 ins with collagenous domains suggesting that MCL1 is a member of a patchily distributed gene family.

261 are dependent only on MCL1, suggesting that MCL1 may have nonredundant functions.

262 Here we show in vitro and in vivo that MCL1 interacts with the cell cycle regulator, proliferat

263 The MCL1 member of the BCL2 family is up-regulated during th

264 on correlated with and directly affected the MCL1 BH3 mimetic S63845 sensitivity of myeloma cells by

265 n composed of sirolimus, venetoclax, and the MCL1 inhibitor S63845.

266 Functional investigations identified the MCL1 gene as a critical downstream effector for BET degr

267 g with a low MCL1:BCL-X(L) ratio; indeed the MCL1:BCL-X(L) ratio is predictive of ERK1/2 pathway inhi

268 phosphatase 1/2A inhibitors also induced the MCL1 band shift/phosphorylation.

269 catalyze dynamic histone acetylation of the MCL1 alternative exon and alter the splicing of MCL1 pre

270 red rapidly and was transient, levels of the MCL1 mRNA being elevated within 4 h and having returned

271 ation events to regulate the turnover of the MCL1 protein and thus its availability for antiapoptotic

272 hese results indicate that expression of the MCL1 viability-enhancing gene is regulated through a cyt

273 val MCL1 gene (3-fold) and overexpressed the MCL1 protein.

274 1/2 inhibitors are synthetic lethal with the MCL1 inhibitor AZD5991, driving profound tumour cell dea

275 Thus, MCL1 inhibition is a promising strategy as both a single

276 Thus, MCL1 undergoes two distinct types of phosphorylation: (i

277 nt mutant of fortilin lacking the binding to MCL1, was significantly shorter than that of wild-type f

278 se complex (CRL5) that resensitized cells to MCL1 inhibition.

279 t the chemotherapeutic drug docetaxel due to MCL1 upregulation but remain sensitive to the PARP inhib

280 discover mechanisms underlying resistance to MCL1 inhibition, we performed multiple flow-cytometry ba

281 high BCL-xL expression confers resistance to MCL1 repression, thereby identifying a patient-selection

282 tient-derived models, assessing responses to MCL1 inhibition.

283 1q arm, we observed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain.

284 Taken together, MCL1 is a regulator of both apoptosis and cell cycle pro

285 These results point towards MCL1 as a target for the treatment of a wide range of tu

286 elanoma biases the pro-survival pool towards MCL1.

287 ycle progression as effectively as wild type MCL1.

288 elta)(4A) was identical to that of wild type MCL1.

289 diminishes the antiapoptotic, long variant (MCL1-L).

290 of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (

291 s, in stroma contact models, and in vivo via MCL1 reduction and by effector caspase activation.

292 or in cancers such as multiple myeloma where MCL1 levels directly correlate to disease progression.

293 s finding prompted us to investigate whether MCL1, in addition to its anti-apoptotic function, has an

294 However, while MCL1 phosphorylation induced by the protein kinase C act

295 ed with nascent pre-mRNA in general and with MCL1 pre-mRNA specifically.

296 gnosis of human NSCLC is not associated with MCL1, despite its overexpression in many NSCLCs.

297 hus combining ERK1/2 pathway inhibitors with MCL1 antagonists in melanoma could improve therapeutic i

298 Fortilin specifically interacted with MCL1 both in vitro and in vivo.

299 screening of a yeast two-hybrid library with MCL1 as bait.

300 ive of ERK1/2 pathway inhibitor synergy with MCL1 or BCL2/BCL-w/BCL-X(L) inhibitors.