ライフサイエンスコーパス: degron

1 ted repertoire of known degradation signals (degrons).

2 proteins act as degradation determinants (N-degrons).

3 correct spacing are insufficient as a KEAP1 degron.

4 ndogenous protein genomically with the auxin degron.

5 old) with the addition of a protease-cleaved degron.

6 of the presence or absence of its N-terminal degron.

7 ires phosphorylation of TFAP4 on a conserved degron.

8 c retention determinant and an Asi-dependent degron.

9 F(Cdc4) after phosphorylation of a multisite degron.

10 post-translationally modified to expose an N-degron.

11 g3, direct ligands of Cog1, can repress this degron.

12 OG complex, is also shown to contain an Ac/N-degron.

13 ryo-EM structures of ClpXP bound to the ssrA degron.

14 ClpS and eluted with a peptide bearing an N-degron.

15 sphorylates and thereby neutralizes the Msh4 degron.

16 FBW7 in a manner independent of a canonical degron.

17 y nascent-chain C termini with a polyalanine degron.

18 C-terminal intracellular domain containing a degron.

19 ollowing recognition of sequence tags called degrons.

20 dation of related substrates with C-terminal degrons.

21 trol (PQC)-specific and compartment-specific degrons.

22 for large-scale identification of eukaryotic degrons.

23 by recognizing their N-terminal or internal degrons.

24 s for specific substrate sequence motifs, or degrons.

25 minantly the destruction (D) box and KEN box degrons.

26 itions that shield and unshield natural Ac/N-degrons.

27 ubstrates bearing ssrA tags or other related degrons.

28 teolytic systems that target N-degrons and C-degrons.

29 and semantic uniformity for N-degrons and C-degrons.

30 ns engineered to contain the auxin-inducible degron (AID) are selectively degraded upon adding auxin.

31 The auxin-inducible degron (AID) system enables rapid depletion of target pr

32 depletion of PICH using the auxin-inducible degron (AID) system resulted in the retention of SUMO2/3

33 ess this question, we apply an Auxin-Induced Degron (AID) system to distinguish roles of basket nucle

34 OP2A in mitosis, we used the auxin-inducible degron (AID) system to rapidly degrade the protein at di

35 The auxin-inducible degron (AID) system was developed as a tool to achieve r

36 d a derivative expressing an auxin-inducible degron (AID)-tagged version of the protein have been use

37 We created a novel Pan1-degron allele, Pan1-AID, in which Pan1 can be specifical

38 Surprisingly, the UBL degron allows for degradation of the most stable sGFP-co

39 To this end, we use a fusion between a degron and an inactivating peptide that can be added to

40 ClpS binds the substrate N-degron and assembles into a high-affinity ClpS-substrate

41 lectively destroyed through attacks by the N-degron and C-degron pathways.

42 presents the shortest cholesterol-responsive degron and enables SM to sense excess cholesterol in the

43 ruction box (D-box) is the most common APC/C degron and plays a crucial role in substrate degradation

44 we mapped the minimal IMiD-responsive IKZF3 degron and show that this peptidic degron can be used to

45 N-degrons and C-degrons are degradation signals whose main

46 addition to being topologically analogous, N-degrons and C-degrons are related functionally.

47 N-degrons and C-degrons include, to varying extents, adjoi

48 functional proteolytic systems that target N-degrons and C-degrons.

49 their brevity and semantic uniformity for N-degrons and C-degrons.

50 How coactivators recognize D box degrons and how this is inhibited by APC/C regulatory pr

51 ate specific degradation signals termed Ac/N-degrons and targeted by the Ac/N-end rule pathway.

52 compared two targeting systems: linear Ub(4) degrons and the UBL domain from yeast Rad23, both of whi

53 lear antigen-interacting protein-degron (PIP-degron) and that knockdown of the components of the CRL4

54 rally, model UPS substrates having different degrons, and aggregation-prone proteins associated with

55 rmation about substrate recognition signals, degrons, and conditional effects.

56 Coactivators recognize substrate degrons, and enhance the affinity of the APC/C for its c

57 3 degron contains two canonical Cdc4 phospho-degrons, and the phosphorylation of each of these is req

58 by many E3s constitute an important class of degrons, and these are almost always present in disorder

59 nd selectivity determinants encoded in APC/C degrons, and we describe some of the extrinsic mechanism

60 In summary, our findings reveal the degron architecture of SM N100, introducing the role of

61 Degrons are also employed as pseudosubstrate motifs by A

62 ylated proteins, in which N-terminal glycine degrons are conditionally exposed after a failure of N-m

63 N-degrons and C-degrons are degradation signals whose main determinants

64 N-terminal glycine degrons are depleted at native N-termini but strongly en

65 Substrates carrying N-degrons are recognized by N-recognins that mediate ubiqu

66 ing topologically analogous, N-degrons and C-degrons are related functionally.

67 Specific N-terminal amino acids (N-degrons) are sufficient to target a protein to the degra

68 y, a set of N-terminal amino acids, called N-degrons, are recognized and ubiquitinated by the UBR pro

69 study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-E

70 We propose that there is a dual degron at the N-terminus of the UmuD protein in Synechoc

71 nd exposed by oxidation do not function as a degron, because they are not sufficient to convert a non

72 Both types of N-degrons bind its ZZ domain.

73 Degron binding regulates the activities of the AAA+ Lon

74 vities, general architectures, and substrate degron-binding modes.

75 Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that ex

76 ive IKZF3 degron and show that this peptidic degron can be used to target heterologous proteins for d

77 in degradation cassette, the low-temperature degron cassette.

78 cence protein modified by carboxyl fusion of degron CL1) and bona fide (CryAB(R120G)) misfolded prote

79 a UPS reporter protein consisting of a short degron, CL1, fused to the COOH-terminus of green fluores

80 providing the first example of a cholesterol-degron collaboration.

81 Deltaubl1 mutant to recognize an N-end rule degron confirmed involvement of UBL1 in the N-end rule p

82 Forced localization of the degron constructs revealed that proteolysis mediated by

83 an be systematically generated via synthetic degron constructs, which facilitates future investigatio

84 The polo kinase Cdc5-derived degron contained an essential KEN motif, whereas a singl

85 The SfIAP degron contains mitogen-activated kinase (MAPK)-like reg

86 The Hst3 degron contains two canonical Cdc4 phospho-degrons, and

87 ted for destruction during S phase via a PIP degron, contributing to oscillations of Dap protein accu

88 Of note, the earliest known Doa10 yeast degron, Deg1, also contains an amphipathic helix and exh

89 Additionally, degron deletion mutants that upregulate Pyr exhibit cell

90 Degron-dependent depletion of Taf1, Taf2, Taf7, Taf11, a

91 density, and does not contact the substrate degron directly.

92 sible for turnover of YfgM and find that the degron does not at all comply with the known N-end rule

93 Mutation of the Hst3 diphospho-degron does not completely stabilize Hst3 in vivo, but i

94 GFP-containing substrates, whereas the Ub(4) degron does not.

95 he GSK3beta-mediated phosphorylation of CHD1 degron domains, which promotes CHD1 degradation via the

96 SCF(Slmb) interacts with a phosphor degron embedded within the human and fruitfly SMN YG-box

97 on the location of their degradation signal/degron: ERAD-L (lumen), ERAD-M (membrane), and ERAD-C (c

98 s the capacity for recognizing intramembrane degrons, expanding its spectrum of substrates.

99 cult-to-unfold substrates, whereas the Ub(4) degron favors clipping.

100 precludes unfolding and degradation; the UBL degron favors degradation of even difficult-to-unfold su

101 e, highlighting the conservation of critical degron features from yeast to humans.

102 Here, we decided to use inducible degrons for a more rapid and comprehensive PRDM14 deplet

103 The effectiveness of degrons for acute protein depletion is widely applicable

104 inds to phosphotyrosine-modified epitopes as degrons for ubiquitination and proteasomal degradation,

105 The sul20 degron from the cell-division inhibitor SulA is shown he

106 Doa10 recognizes the Deg1 degron from the MATalpha2 transcription factor.

107 Whereas ubiquitin-dependent degrons have been characterized in some detail, how prot

108 A variety of alternative APC/C degrons have been reported, suggesting either that multi

109 However, repositioning of AD2-adjoining degrons (i.e. DSGLS-containing SDS1 and PEST2 sequences)

110 Here we describe an entirely new degron identified in the cytoplasmic N-terminal end of t

111 represent the shortest cholesterol-regulated degron identified to date.

112 estroyed via its activated (unshielded) Ac/N-degron if the total level of Cog1 increased in a cell.

113 to the SPOP-mediated degradation because of degron impairment.

114 ymphomas, aggregate within an amino-terminal degron important for proteasomal destruction of MYC, and

115 We determine that ClpS recognizes a type of degron in intact proteins based on the identity of the f

116 Additional HOX paralogs share the conserved degron in the homeodomain and are also subject to CUL4-m

117 re detail in vivo we used an auxin inducible degron in which Mcm10 is degraded upon addition of auxin

118 Here the authors show that p62 recognises N-degrons in these proteins, acting as a N-recognin from t

119 Furthermore, the absence of analogous degrons in virus-encoded IAPs explains their relative st

120 t complex can create, at the same time, an N-degron (in a C-terminal fragment) and a spatially adjace

121 erminal fragment) and a spatially adjacent C-degron (in an N-terminal fragment).

122 To identify the ClpX degradation tag (degron) in HsdR, we used bioinformatics and biochemical

123 N-degrons and C-degrons include, to varying extents, adjoining sequence

124 inds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg).

125 hosphorylation of Thr464 present in the CDT2 degron inhibits recognition by FBXO11.

126 C-terminal residues of the ssrA degron initially bind in the top of an otherwise closed

127 ubstrates, support a model in which the ssrA degron initially binds in the top portion of the axial c

128 The YfgM degron is a distinct module that facilitates FtsH-mediat

129 erated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment

130 Our findings support a model wherein the degron is exposed when SMN is monomeric and sequestered

131 interaction of TDG with PCNA through the PIP degron is required for targeting TDG to the CRL4(Cdt2) E

132 y ClpS-substrate-ClpA complex, but how the N-degron is transferred from ClpS to the axial pore of the

133 The Degron-KI system allows for highly specific, inducible,

134 results demonstrate the broad utility of the Degron-KI system for the functional characterization of

135 The Degron-KI system was able to faithfully recapitulate the

136 -mediated knock-in of inducible degron tags (Degron-KI) that provides a versatile approach for the fu

137 Degron-like sequences of the MCC subunit BubR1 block deg

138 The degron likely responds to virus-induced kinase-specific

139 Molecules containing hydrophobic degrons linked to small-molecule AR ligands induce AR de

140 Intriguingly, the degron maps to the Sbh2 TM region.

141 ptides or becomes limiting, CAT tails act as degrons, marking proteins for proteasomal degradation of

142 Degron-mediated depletion of NHR-23/NR1F1 within hermaph

143 y the result of viral IAP evolution in which degron-mediated destabilization and ubiquitination poten

144 CDK2-related kinase) as required for LIN-45 degron-mediated turnover.

145 egradation of wild-type ERG by recognizing a degron motif at the N terminus of ERG.

146 teins (BRD2, BRD3 and BRD4) by recognizing a degron motif common among them.

147 tions increase affinity between TIR1 and the degron motif of Aux/IAAs and enhance the activity of the

148 the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired t

149 Interaction between the phosphorylated degron motif of TRIM9 and the WD40 repeat region of beta

150 Biochemical analysis of the degron motif recognized by MAGE-A11 and the crystal stru

151 cally interacts with SPOP via a conservative degron motif.

152 ate specificity arises from binding of short degron motifs in its substrates to transient activator s

153 mulation required activator interaction with degron motifs on the substrate.

154 Although well characterized degron motifs such as the destruction box (D-box) and KE

155 alysis confirmed this interaction and mapped degron motifs within ASPP2, which are required for Siah2

156 f full-length SMN are also stabilized in the degron mutant background.

157 Expression of a PIP degron mutant Dap attenuates endocycle progression but d

158 e motif in IAA28 resembled plants expressing degron mutations, underscoring the functional relevance

159 gnin that binds type-1 and type-2 N-terminal degrons (N-degrons), including arginine (Nt-Arg).

160 Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endop

161 hway, which recognized a C terminus-proximal degron of Chk1.

162 mide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradatio

163 We conclude that the O(2) -sensitive N-degron of VRN2 has a dual function, confining VRN2 to me

164 and define the degradation signal sequence (degron) of HOXB4 required for CUL4-mediated destruction.

165 ctive for crossing over due to an N-terminal degron on Msh4 that renders it unstable by directly targ

166 recognizes short linear sequence motifs, or degrons, on its substrates.

167 g different repressible promoters, inducible degrons, or their combinations were developed.

168 protein degradation via the N-end rule or N-degron pathway and has been used to vice versa accumulat

169 ERFVII proteolysis is regulated by the N-degron pathway and mediates adaptation to flooding-induc

170 ir mRNAs, strongly suggesting that the Arg/N-degron pathway can also modulate translation of specific

171 The current concept holds that the N-degron pathway depends on the identity of the amino (N)-

172 of oxygen availability through the Cys/Arg N-degron pathway functions alongside ROS production and si

173 The ClpS protein enforces the N-degron pathway in bacteria and bacteria-derived organell

174 gen-regulated stability of proteins by the N-degron pathway in human cells.

175 possible entry point for substrates of the N-degron pathway is oxidation of N-terminal Cys residues.

176 ansferase 1 (Ate1), a component of the Arg/N-degron pathway of protein degradation.

177 lated target of the PCO branch of the PRT6 N-degron pathway of ubiquitin-mediated proteolysis.

178 Thus, an additional N-degron pathway specific for glycine regulates the stabil

179 The Arg/N-degron pathway targets proteins for degradation by recog

180 The Arg/N-degron pathway targets proteins for degradation by recog

181 e N-end rule pathway (recently renamed the N-degron pathway).

182 The N-degron pathway, formerly the N-end rule pathway, regulat

183 ted into transcriptional regulation by the N-degron pathway, thereby linking the control of metabolic

184 n pathway-part of the PROTEOLYSIS 6 (PRT6)/N-degron pathway-as well as the underlying physiological p

185 degradation via the Cys/Arg branch of the N-degron pathway-part of the PROTEOLYSIS 6 (PRT6)/N-degron

186 onent (N-recognin) of the GID-mediated Pro/N-degron pathway.

187 heir degradation by the Gid4-dependent Pro/N-degron pathway.

188 1 and UBR2 E3 ubiquitin ligases of the Arg/N-degron pathway.

189 GR is a physiological substrate of the Arg/N-degron pathway.

190 degradation via the Cys/Arg branch of the N-degron pathway.

191 in fragments are genuine substrates of the N-degron pathway.

192 nction as a specific N-recognin of the Pro/N-degron pathway.

193 ot meristem inhibits the proteolysis of an N-degron-pathway(4,5) substrate known as LITTLE ZIPPER 2 (

194 In eukaryotes, N-degron pathways (formerly "N-end rule pathways") compris

195 The proteolytic systems known as the N-degron pathways recognize signals at the N terminus of p

196 e also propose to denote these systems as "N-degron pathways" and "C-degron pathways." The former not

197 troyed through attacks by the N-degron and C-degron pathways.

198 sidue influences protein stability through N-degron pathways.

199 to uncover multiple additional features of N-degron pathways.

200 these systems as "N-degron pathways" and "C-degron pathways." The former notation replaces the earli

201 Binding of acetylated degron peptides to CRBN depends on an intact thalidomide

202 ing cell nuclear antigen-interacting protein-degron (PIP-degron) and that knockdown of the components

203 in mechanical protein degradation, show that degron placement can change whether unfolding or translo

204 ning N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby c

205 ning N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby c

206 lows ClpXP to check potential substrates for degrons, potentially increasing specificity.

207 residues essential for the action of the PIP degron prevent the ubiquitination and degradation of TDG

208 For short-degron protein substrates, we show that unfolding can oc

209 ansmembrane proteins with the photosensitive degron (psd) module resulted in light-dependent degradat

210 nd substrate HspQ into an inhibitor of the N-degron recognin ClpS, the adaptor of the ClpAP protease.

211 y and physiological role of the widespread N-degron recognin ClpS.

212 ike sequences of the MCC subunit BubR1 block degron recognition sites on Cdc20, the APC/C coactivator

213 d be associated with protein degradation and degron recognition.

214 n two conserved ClpS1 residues involved in N-degron recognition.

215 llin-RING catalytic subunits relative to the degron-recognition module of coactivator and APC10.

216 ng C-terminal poly-alanine tails that act as degrons recognized by the ClpXP protease.

217 strates and discuss that substrate elements (degrons) recognized by E3 ligases are highly disordered:

218 hown to be orthogonal and active in exposing degrons, releasing inhibitory domains and cleaving polyp

219 undamental intrinsic characteristics of this degron remain unknown.

220 stis sp. PCC6803, which is distinct from the degron required for degradation of UmuD in E. coli.

221 our findings suggest that the SfIAP phospho-degron responds rapidly to a signal-activated kinase cas

222 d we demonstrate that this regulation of the degron's activity is critical for IkappaBalpha's signali

223 Finally, we show that this degron's activity is regulated by the interaction with N

224 er-derived mutations in SPOP or at the Nanog-degron (S68Y) disrupt SPOP-mediated destruction of Nanog

225 s is likely to be modulated by variations in degron sequence and context.

226 Tiam1 to the F-box protein betaTrCP via its degron sequence and subsequent Tiam1 ubiquitylation and

227 DMRT1 contains a consensus beta-TrCP degron sequence that was found to bind beta-TrCP.

228 r, these results identify the first specific degron sequence within a native i-AAA protease substrate

229 Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulat

230 ed stability of SUB1A-1 despite bearing an N-degron sequence.

231 The juxtaposition of degron sequences and E2F interaction motifs appears to b

232 get proteins generally have D-Box or KEN-Box degron sequences.

233 age-specific targeting of SAMHD1 N-terminal "degron" sequences.

234 ion of CK1 and MEK, or mutation of the Tiam1 degron site.

235 osolic protein DeltaMTS-Aco1 tagged with the degron SL17 (a ubiquitin-proteasome substrate).

236 Fusion of the degron (SlNAC1(191-270) ) containing these 10 amino acid

237 phagy through its binding Nt-Arg and other N-degrons.Soluble misfolded proteins that fail to be degra

238 tion are possible or that our definitions of degron structure are incomplete.

239 Bacterial ClpS is involved in N-degron substrate selection and delivery to the ClpAP pro

240 The ClpS adaptor delivers N-degron substrates to ClpAP but inhibits degradation of s

241 on, specific features of protein-sized Arg/N-degron substrates, including their partly sequential and

242 RGS4/5 (regulator of G protein signaling) N-degron substrates, modulates G protein-coupled calcium i

243 For longer degron substrates, our studies illuminate how ClpXP tran

244 A+ ClpAP protease to recognize and degrade N-degron substrates.

245 location of these substrates as well as of N-degron substrates.

246 fail to identify a single degradation motif (degron) sufficient for DnaA degradation, rather we show

247 e we describe minimal degradation sequences (degrons) sufficient for rapid APC/C-Cdh1-specific in viv

248 uced a phenotype consistent with loss of the degron, suggesting an as-yet-unidentified recognition pa

249 FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is

250 In summary, we show that an auxin-dependent degron system can be used to rapidly deplete nucleolar p

251 Using the auxin-inducible degron system in mouse embryonic stem cells, we show tha

252 nd resection in vivo, using a heat-inducible degron system that allows rapid conditional depletion of

253 Using an inducible auxin-degron system to rapidly deplete RPB1 (the largest subun

254 eously eliminated, using the auxin-inducible degron system.

255 iption factor (ARF) in an improved inducible degron system.

256 etion of CTCF protein by the auxin-inducible degron system.

257 ssessment using Smc5 cKO and auxin-inducible degron systems demonstrated that absence of SMC5/6 leads

258 The degron tag can be efficiently introduced by CRISPR/Cas9-

259 is(6), mCherry, GFP, and the auxin-inducible degron tag for compound-induced protein depletion.

260 isms and facilitate elimination of native or degron-tagged proteins from cells are rapidly emerging.

261 mediates robust auxin-dependent depletion of degron-tagged targets.

262 r CRISPR/Cas9-mediated knock-in of inducible degron tags (Degron-KI) that provides a versatile approa

263 Using degron tags for rapid inducible protein removal, we anal

264 proteasome, suggesting an even larger Arg/N-degron-targeting complex that contains the proteasome as

265 xpression, we integrated the auxin-inducible degron technology with CRISPR tools.

266 n plants to characterize motifs flanking the degron that contribute to tuning the dynamics of Aux/IAA

267 combining CRISPR/Cas9 and an auxin-inducible degron that enables combining a "genetics-like"approach

268 re, we identify and characterize the minimal degron that encompasses the CPD and is sufficient for SE

269 acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and

270 This creates a diphosphorylated degron that is necessary for Hst3 polyubiquitylation by

271 the APC/C ubiquitin ligase, contains an Ac/N-degron that is repressed by Cut9, another APC/C subunit

272 cyclin C-Cdk8 association and serves as the degron that mediates ubiquitin ligase SCF(Grr1)-dependen

273 bilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-

274 verse insects carry unique signal-responsive degrons that control IAP turnover.

275 Many of these create degradation signals (N-degrons) that mediate protein destruction via the N-end

276 trates contain recognition motifs, so-called degrons, that direct them to the appropriate protease.

277 , and sequences outside of the characterized degron (the minimum region required for auxin-induced de

278 Functioning as a protein degron, the cellular IAP leader dramatically shortened t

279 In both degrons, the APC/C recognition motif was flanked by a nu

280 ning N-terminal degradation signals called N-degrons, thereby causing degradation of these proteins b

281 Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurre

282 ere, we used SM N100 fused to GFP as a model degron to recapitulate cholesterol-mediated SM degradati

283 ion, and a system using CRY2 and a LOV-fused degron to simultaneously block transcription and deplete

284 es stalled ribosomes and adds an ssrA tag or degron to the C-terminus of the incomplete protein, whic

285 -box, and the recently identified ABBA motif degrons to Cdh1.

286 ploy the demonstrated conditionality of Ac/N-degrons to regulate subunit stoichiometries and other as

287 -1V or ANDV GnTs and that mutations that add degrons to TULV or PHV GnTs confer TRAF3 binding.

288 These findings define a structural degron underlying cereblon 'neosubstrate' selectivity, a

289 A particularly large set of C-degrons was discovered in 2018.

290 t degradation of proteins with intramembrane degrons was largely unperturbed by ER stress.

291 SOD1 binds a C-terminal degron we identified in Yck1p/Yck2p and promotes kinase

292 Discovered in 1986, N-degrons were the first degradation signals in short-live

293 ltiple destabilization factors and acts as a degron when fused to other proteins.

294 mma is abolished by removal of SDS1 or PEST2 degrons, whereas production of the cleaved 85-kDa Nrf1 i

295 CRL4(Cdt2) targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclea

296 appaBalpha contains an ubiquitin-independent degron whose activity is portable to heterologous protei

297 Lon recognizes HspQ via a C-terminal degron, whose precise presentation, in synergy with mult

298 led by a conserved phosphorylation-sensitive degron within the IAP N-terminal leader.

299 Degrons within AD1 do not promote proteolytic degradatio

300 T binding to TRAF3 is mediated by C-terminal degrons within NY-1V or ANDV GnTs and that mutations tha