                         SEQUENCE LISTING

<110>  CELGENE CORPORATION
 
<120>  COMPOSITIONS AND METHODS FOR INDUCING CONFORMATIONAL CHANGES IN 
       CEREBLON AND OTHER E3 UBIQUITIN LIGASES

<130>  12827-980-228

<140>  PCT/US16/68697
<141>  2016-12-27

<150>  US 62/271,864
<151>  2015-12-28

<160>  24    

<170>  PatentIn version 3.5

<210>  1
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Degron sequence

<220>
<221>  VARIANT
<222>  (1)..(1)
<223>  Xaa is ASP or ASN

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  VARIANT
<222>  (4)..(4)
<223>  Xaa is Ser or Thr

<400>  1

Xaa Xaa Xaa Xaa Gly 
1               5   


<210>  2
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A first exemplary degron sequence

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  2

Asp Xaa Xaa Ser Gly 
1               5   


<210>  3
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A second  exemplary degron sequence

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  3

Asn Xaa Xaa Ser Gly 
1               5   


<210>  4
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A third  exemplary degron sequence

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  4

Asp Xaa Xaa Thr Gly 
1               5   


<210>  5
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A fourth  exemplary degron sequence

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  5

Asn Xaa Xaa Thr Gly 
1               5   


<210>  6
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A fifth  exemplary degron sequence

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  6

Cys Xaa Xaa Cys Gly 
1               5   


<210>  7
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A sixth   exemplary degron sequence

<220>
<221>  misc_feature
<222>  (2)..(3)
<223>  Xaa can be any naturally occurring amino acid

<400>  7

Asn Xaa Xaa Asn Gly 
1               5   


<210>  8
<211>  60
<212>  PRT
<213>  Homo sapiens

<220>
<223>  Agent binding domain of CRBN of Homo

<400>  8

Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Cys Asn Leu Asn Leu 
1               5                   10                  15      


Ile Gly Arg Pro Ser Thr Glu His Ser Trp Phe Pro Gly Tyr Ala Trp 
            20                  25                  30          


Thr Val Ala Gln Cys Lys Ile Cys Ala Ser His Ile Gly Trp Lys Phe 
        35                  40                  45              


Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe 
    50                  55                  60  


<210>  9
<211>  60
<212>  PRT
<213>  Macaca

<220>
<223>  Agent binding domain of CRBN of Macaca

<400>  9

Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Cys Asn Leu Asn Leu 
1               5                   10                  15      


Ile Gly Arg Pro Ser Thr Glu His Ser Trp Phe Pro Gly Tyr Ala Trp 
            20                  25                  30          


Thr Val Ala Gln Cys Lys Ile Cys Ala Ser His Ile Gly Trp Lys Phe 
        35                  40                  45              


Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe 
    50                  55                  60  


<210>  10
<211>  60
<212>  PRT
<213>  Mus

<220>
<223>  Agent binding domain of CRBN of Mus

<400>  10

Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Ser Asn Leu Asn Leu 
1               5                   10                  15      


Ile Gly Arg Pro Ser Thr Val His Ser Trp Phe Pro Gly Tyr Ala Trp 
            20                  25                  30          


Thr Ile Ala Gln Cys Lys Ile Cys Ala Ser His Ile Gly Trp Lys Phe 
        35                  40                  45              


Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe 
    50                  55                  60  


<210>  11
<211>  60
<212>  PRT
<213>  Rattus

<220>
<223>  Agent binding domain of CRBN of Rattus

<400>  11

Tyr Val His Glu Thr Leu Thr Val Tyr Lys Ala Ser Asn Leu Asn Leu 
1               5                   10                  15      


Ile Gly Arg Pro Ser Thr Val His Ser Trp Phe Pro Gly Tyr Ala Trp 
            20                  25                  30          


Thr Ile Ala Gln Cys Lys Ile Cys Ala Ser His Ile Gly Trp Lys Phe 
        35                  40                  45              


Thr Ala Thr Lys Lys Asp Met Ser Pro Gln Lys Phe 
    50                  55                  60  


<210>  12
<211>  62
<212>  PRT
<213>  Drosophila

<220>
<223>  Agent binding domain of CRBN of Drosophila

<400>  12

Tyr Ile His Glu Thr Asn Thr Val Tyr Arg Val Ile Ser His Ala Ile 
1               5                   10                  15      


Gly Tyr Ser Gly Glu Pro Ser Thr Lys Phe Ser Trp Phe Pro Gly Tyr 
            20                  25                  30          


Gln Trp His Ile Ile Leu Cys Lys Phe Cys Ala Gln His Val Gly Trp 
        35                  40                  45              


Glu Phe Lys Ala Val His Pro Asn Leu Thr Pro Lys Asn Phe 
    50                  55                  60          


<210>  13
<211>  60
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Agent binding domain of CRBN of Glycine max

<400>  13

Tyr Val His Glu Ile Met Thr Leu Tyr Lys Ala Asn Gly Leu Ala Leu 
1               5                   10                  15      


Val Gly Ser Ala Ala Thr Asp Tyr Ser Trp Phe Pro Gly Tyr Ala Trp 
            20                  25                  30          


Thr Ile Ala Thr Cys Ala Thr Cys Lys Thr Gln Met Gly Trp Leu Phe 
        35                  40                  45              


Thr Ala Arg Asn Lys Gln Leu Lys Pro Ser Tyr Phe 
    50                  55                  60  


<210>  14
<211>  637
<212>  PRT
<213>  Homo sapiens

<220>
<223>  Human GSPT1

<400>  14

Met Asp Pro Gly Ser Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly 
1               5                   10                  15      


Ser Ser Ser Gly Ser Ser Ser Ser Asp Ser Ala Pro Asp Cys Trp Asp 
            20                  25                  30          


Gln Ala Asp Met Glu Ala Pro Gly Pro Gly Pro Cys Gly Gly Gly Gly 
        35                  40                  45              


Ser Leu Ala Ala Ala Ala Glu Ala Gln Arg Glu Asn Leu Ser Ala Ala 
    50                  55                  60                  


Phe Ser Arg Gln Leu Asn Val Asn Ala Lys Pro Phe Val Pro Asn Val 
65                  70                  75                  80  


His Ala Ala Glu Phe Val Pro Ser Phe Leu Arg Gly Pro Ala Ala Pro 
                85                  90                  95      


Pro Pro Pro Ala Gly Gly Ala Ala Asn Asn His Gly Ala Gly Ser Gly 
            100                 105                 110         


Ala Gly Gly Arg Ala Ala Pro Val Glu Ser Ser Gln Glu Glu Gln Ser 
        115                 120                 125             


Leu Cys Glu Gly Ser Asn Ser Ala Val Ser Met Glu Leu Ser Glu Pro 
    130                 135                 140                 


Ile Val Glu Asn Gly Glu Thr Glu Met Ser Pro Glu Glu Ser Trp Glu 
145                 150                 155                 160 


His Lys Glu Glu Ile Ser Glu Ala Glu Pro Gly Gly Gly Ser Leu Gly 
                165                 170                 175     


Asp Gly Arg Pro Pro Glu Glu Ser Ala His Glu Met Met Glu Glu Glu 
            180                 185                 190         


Glu Glu Ile Pro Lys Pro Lys Ser Val Val Ala Pro Pro Gly Ala Pro 
        195                 200                 205             


Lys Lys Glu His Val Asn Val Val Phe Ile Gly His Val Asp Ala Gly 
    210                 215                 220                 


Lys Ser Thr Ile Gly Gly Gln Ile Met Tyr Leu Thr Gly Met Val Asp 
225                 230                 235                 240 


Lys Arg Thr Leu Glu Lys Tyr Glu Arg Glu Ala Lys Glu Lys Asn Arg 
                245                 250                 255     


Glu Thr Trp Tyr Leu Ser Trp Ala Leu Asp Thr Asn Gln Glu Glu Arg 
            260                 265                 270         


Asp Lys Gly Lys Thr Val Glu Val Gly Arg Ala Tyr Phe Glu Thr Glu 
        275                 280                 285             


Lys Lys His Phe Thr Ile Leu Asp Ala Pro Gly His Lys Ser Phe Val 
    290                 295                 300                 


Pro Asn Met Ile Gly Gly Ala Ser Gln Ala Asp Leu Ala Val Leu Val 
305                 310                 315                 320 


Ile Ser Ala Arg Lys Gly Glu Phe Glu Thr Gly Phe Glu Lys Gly Gly 
                325                 330                 335     


Gln Thr Arg Glu His Ala Met Leu Ala Lys Thr Ala Gly Val Lys His 
            340                 345                 350         


Leu Ile Val Leu Ile Asn Lys Met Asp Asp Pro Thr Val Asn Trp Ser 
        355                 360                 365             


Asn Glu Arg Tyr Glu Glu Cys Lys Glu Lys Leu Val Pro Phe Leu Lys 
    370                 375                 380                 


Lys Val Gly Phe Asn Pro Lys Lys Asp Ile His Phe Met Pro Cys Ser 
385                 390                 395                 400 


Gly Leu Thr Gly Ala Asn Leu Lys Glu Gln Ser Asp Phe Cys Pro Trp 
                405                 410                 415     


Tyr Ile Gly Leu Pro Phe Ile Pro Tyr Leu Asp Asn Leu Pro Asn Phe 
            420                 425                 430         


Asn Arg Ser Val Asp Gly Pro Ile Arg Leu Pro Ile Val Asp Lys Tyr 
        435                 440                 445             


Lys Asp Met Gly Thr Val Val Leu Gly Lys Leu Glu Ser Gly Ser Ile 
    450                 455                 460                 


Cys Lys Gly Gln Gln Leu Val Met Met Pro Asn Lys His Asn Val Glu 
465                 470                 475                 480 


Val Leu Gly Ile Leu Ser Asp Asp Val Glu Thr Asp Thr Val Ala Pro 
                485                 490                 495     


Gly Glu Asn Leu Lys Ile Arg Leu Lys Gly Ile Glu Glu Glu Glu Ile 
            500                 505                 510         


Leu Pro Gly Phe Ile Leu Cys Asp Pro Asn Asn Leu Cys His Ser Gly 
        515                 520                 525             


Arg Thr Phe Asp Ala Gln Ile Val Ile Ile Glu His Lys Ser Ile Ile 
    530                 535                 540                 


Cys Pro Gly Tyr Asn Ala Val Leu His Ile His Thr Cys Ile Glu Glu 
545                 550                 555                 560 


Val Glu Ile Thr Ala Leu Ile Cys Leu Val Asp Lys Lys Ser Gly Glu 
                565                 570                 575     


Lys Ser Lys Thr Arg Pro Arg Phe Val Lys Gln Asp Gln Val Cys Ile 
            580                 585                 590         


Ala Arg Leu Arg Thr Ala Gly Thr Ile Cys Leu Glu Thr Phe Lys Asp 
        595                 600                 605             


Phe Pro Gln Met Gly Arg Phe Thr Leu Arg Asp Glu Gly Lys Thr Ile 
    610                 615                 620                 


Ala Ile Gly Lys Val Leu Lys Leu Val Pro Glu Lys Asp 
625                 630                 635         


<210>  15
<211>  685
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Yeast SUP35

<400>  15

Met Ser Asp Ser Asn Gln Gly Asn Asn Gln Gln Asn Tyr Gln Gln Tyr 
1               5                   10                  15      


Ser Gln Asn Gly Asn Gln Gln Gln Gly Asn Asn Arg Tyr Gln Gly Tyr 
            20                  25                  30          


Gln Ala Tyr Asn Ala Gln Ala Gln Pro Ala Gly Gly Tyr Tyr Gln Asn 
        35                  40                  45              


Tyr Gln Gly Tyr Ser Gly Tyr Gln Gln Gly Gly Tyr Gln Gln Tyr Asn 
    50                  55                  60                  


Pro Asp Ala Gly Tyr Gln Gln Gln Tyr Asn Pro Gln Gly Gly Tyr Gln 
65                  70                  75                  80  


Gln Tyr Asn Pro Gln Gly Gly Tyr Gln Gln Gln Phe Asn Pro Gln Gly 
                85                  90                  95      


Gly Arg Gly Asn Tyr Lys Asn Phe Asn Tyr Asn Asn Asn Leu Gln Gly 
            100                 105                 110         


Tyr Gln Ala Gly Phe Gln Pro Gln Ser Gln Gly Met Ser Leu Asn Asp 
        115                 120                 125             


Phe Gln Lys Gln Gln Lys Gln Ala Ala Pro Lys Pro Lys Lys Thr Leu 
    130                 135                 140                 


Lys Leu Val Ser Ser Ser Gly Ile Lys Leu Ala Asn Ala Thr Lys Lys 
145                 150                 155                 160 


Val Gly Thr Lys Pro Ala Glu Ser Asp Lys Lys Glu Glu Glu Lys Ser 
                165                 170                 175     


Ala Glu Thr Lys Glu Pro Thr Lys Glu Pro Thr Lys Val Glu Glu Pro 
            180                 185                 190         


Val Lys Lys Glu Glu Lys Pro Val Gln Thr Glu Glu Lys Thr Glu Glu 
        195                 200                 205             


Lys Ser Glu Leu Pro Lys Val Glu Asp Leu Lys Ile Ser Glu Ser Thr 
    210                 215                 220                 


His Asn Thr Asn Asn Ala Asn Val Thr Ser Ala Asp Ala Leu Ile Lys 
225                 230                 235                 240 


Glu Gln Glu Glu Glu Val Asp Asp Glu Val Val Asn Asp Met Phe Gly 
                245                 250                 255     


Gly Lys Asp His Val Ser Leu Ile Phe Met Gly His Val Asp Ala Gly 
            260                 265                 270         


Lys Ser Thr Met Gly Gly Asn Leu Leu Tyr Leu Thr Gly Ser Val Asp 
        275                 280                 285             


Lys Arg Thr Ile Glu Lys Tyr Glu Arg Glu Ala Lys Asp Ala Gly Arg 
    290                 295                 300                 


Gln Gly Trp Tyr Leu Ser Trp Val Met Asp Thr Asn Lys Glu Glu Arg 
305                 310                 315                 320 


Asn Asp Gly Lys Thr Ile Glu Val Gly Lys Ala Tyr Phe Glu Thr Glu 
                325                 330                 335     


Lys Arg Arg Tyr Thr Ile Leu Asp Ala Pro Gly His Lys Met Tyr Val 
            340                 345                 350         


Ser Glu Met Ile Gly Gly Ala Ser Gln Ala Asp Val Gly Val Leu Val 
        355                 360                 365             


Ile Ser Ala Arg Lys Gly Glu Tyr Glu Thr Gly Phe Glu Arg Gly Gly 
    370                 375                 380                 


Gln Thr Arg Glu His Ala Leu Leu Ala Lys Thr Gln Gly Val Asn Lys 
385                 390                 395                 400 


Met Val Val Val Val Asn Lys Met Asp Asp Pro Thr Val Asn Trp Ser 
                405                 410                 415     


Lys Glu Arg Tyr Asp Gln Cys Val Ser Asn Val Ser Asn Phe Leu Arg 
            420                 425                 430         


Ala Ile Gly Tyr Asn Ile Lys Thr Asp Val Val Phe Met Pro Val Ser 
        435                 440                 445             


Gly Tyr Ser Gly Ala Asn Leu Lys Asp His Val Asp Pro Lys Glu Cys 
    450                 455                 460                 


Pro Trp Tyr Thr Gly Pro Thr Leu Leu Glu Tyr Leu Asp Thr Met Asn 
465                 470                 475                 480 


His Val Asp Arg His Ile Asn Ala Pro Phe Met Leu Pro Ile Ala Ala 
                485                 490                 495     


Lys Met Lys Asp Leu Gly Thr Ile Val Glu Gly Lys Ile Glu Ser Gly 
            500                 505                 510         


His Ile Lys Lys Gly Gln Ser Thr Leu Leu Met Pro Asn Lys Thr Ala 
        515                 520                 525             


Val Glu Ile Gln Asn Ile Tyr Asn Glu Thr Glu Asn Glu Val Asp Met 
    530                 535                 540                 


Ala Met Cys Gly Glu Gln Val Lys Leu Arg Ile Lys Gly Val Glu Glu 
545                 550                 555                 560 


Glu Asp Ile Ser Pro Gly Phe Val Leu Thr Ser Pro Lys Asn Pro Ile 
                565                 570                 575     


Lys Ser Val Thr Lys Phe Val Ala Gln Ile Ala Ile Val Glu Leu Lys 
            580                 585                 590         


Ser Ile Ile Ala Ala Gly Phe Ser Cys Val Met His Val His Thr Ala 
        595                 600                 605             


Ile Glu Glu Val His Ile Val Lys Leu Leu His Lys Leu Glu Lys Gly 
    610                 615                 620                 


Thr Asn Arg Lys Ser Lys Lys Pro Pro Ala Phe Ala Lys Lys Gly Met 
625                 630                 635                 640 


Lys Val Ile Ala Val Leu Glu Thr Glu Ala Pro Val Cys Val Glu Thr 
                645                 650                 655     


Tyr Gln Asp Tyr Pro Gln Leu Gly Arg Phe Thr Leu Arg Asp Gln Gly 
            660                 665                 670         


Thr Thr Ile Ala Ile Gly Lys Ile Val Lys Ile Ala Glu 
        675                 680                 685 


<210>  16
<211>  35
<212>  PRT
<213>  Homo sapiens

<220>
<223>  A sequence of human GSPT1

<400>  16

Glu Glu Val Glu Ile Thr Ala Leu Ile Cys Leu Val Asp Lys Lys Ser 
1               5                   10                  15      


Gly Glu Lys Ser Lys Thr Arg Pro Arg Phe Val Lys Gln Asp Gln Val 
            20                  25                  30          


Cys Ile Ala 
        35  


<210>  17
<211>  35
<212>  PRT
<213>  Mus

<220>
<223>  A sequence of mouse GSPT1

<400>  17

Glu Glu Val Glu Ile Thr Ala Leu Ile Cys Leu Val Asp Lys Lys Ser 
1               5                   10                  15      


Gly Glu Lys Ser Lys Thr Arg Pro Arg Phe Val Lys Gln Asp Gln Val 
            20                  25                  30          


Cys Ile Ala 
        35  


<210>  18
<211>  35
<212>  PRT
<213>  Homo sapiens

<220>
<223>  A sequence of human GSPT2

<400>  18

Glu Glu Val Glu Ile Thr Ala Leu Ile Ser Leu Val Asp Lys Lys Ser 
1               5                   10                  15      


Gly Glu Lys Ser Lys Thr Arg Pro Arg Phe Val Lys Gln Asp Gln Val 
            20                  25                  30          


Cys Ile Ala 
        35  


<210>  19
<211>  35
<212>  PRT
<213>  Mus
<220>
<223>  A sequence of mouse GSPT2

<400>  19

Glu Glu Val Glu Ile Thr Ala Leu Ile Ser Leu Val Asp Lys Lys Ser 
1               5                   10                  15      


Gly Glu Lys Ser Lys Thr Arg Pro Arg Phe Val Lys Gln Asp Gln Val 
            20                  25                  30          


Cys Ile Ala 
        35  


<210>  20
<211>  35
<212>  PRT
<213>  Homo sapiens

<220>
<223>  A sequence of human HBS1L

<400>  20

Glu Pro Ala Val Ile Lys Arg Leu Ile Ser Val Leu Asn Lys Ser Thr 
1               5                   10                  15      


Gly Glu Val Thr Lys Lys Lys Pro Lys Phe Leu Thr Lys Gly Gln Asn 
            20                  25                  30          


Ala Leu Val 
        35  


<210>  21
<211>  35
<212>  PRT
<213>  Mus

<220>
<223>  A sequence of mouse HBSIL

<400>  21

Glu Pro Ala Val Ile Lys Arg Leu Ile Ser Val Leu Asn Lys Ser Thr 
1               5                   10                  15      


Gly Glu Val Thr Lys Lys Lys Pro Lys Leu Leu Thr Lys Gly Gln Asn 
            20                  25                  30          


Ala Leu Val 
        35  


<210>  22
<211>  35
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  A sequence of yeast SUP35

<400>  22

Glu Glu Val His Ile Val Lys Leu Leu His Lys Leu Glu Lys Gly Thr 
1               5                   10                  15      


Asn Arg Lys Ser Lys Lys Pro Pro Ala Phe Ala Lys Lys Gly Met Lys 
            20                  25                  30          


Val Ile Ala 
        35  


<210>  23
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  An anchoring motif of GSPT1

<400>  23

Val Asp Lys Lys Ser Gly Glu 
1               5           


<210>  24
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  An anchoring motif of IKAROS

<400>  24

Gln Cys Asn Gln Cys Gly Ala 
1               5           


