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Table 1 Proteolytic cleavage of autoantigens during apoptosis

From: Death, autoantigen modifications, and tolerance

Autoantigen

Function

Cleavage site

Protease

Fragment size

Disease

References

Actin

Cytoskeleton

LVID11, ELPD244

1

41,30,14

Autoimmune Hepatitis

[95]

Alanyl tRNA synthetase

Translation

(VAPD632)

GB

58

PM/DM, ILD

[18*,51**]

CENP-B

Centromere protein

(VDSD457)

GB

58,40

Scleroderma

[18*,51**]

DNA-PK

DNA repair

DEVD2712

3

250,165

SLE, Scleroderma,

[37*,96]

  

VGPD2698

GB

250,150

Overlap Syndrome

[69**]

Fibrillarin

snoRNP protein

VGPD184

GB

37

SLE, Scleroderma, Overlap Syndrome

[51**]

α-Fodrin

Actin binding protein

?

Caspases

150,120

Sjögren's Syndrome

[97]

   

Calpain

   

Histidyl tRNA synthetase

Translation

(LGPD48)

GB

40

PM, ILD, DM, Overlap Syndrome

[18*,51**]

Histone H3

DNA core protein

RKQL20A

FMDV 3Cpro

13

SLE

[86]

hnRNP A1

RNA processing

?

?

32,29,16

SLE, RA, MCTD

[34,98]

hnRNP C1

RNA processing

?

3,6,7

40

Scleroderma, Psoriasis

[99]

hnRNP C2

RNA processing

?

3,6,7

40

Scleroderma, Psoriasis

[99]

hsp-90

Stress response

(DEED259)

?

54

SLE

[18*,100]

Isoleucyl tRNA synthetase

Translation

(VTPD983)

GB

?

PM/DM, ILD

[18*,51**]

Keratin

Cytoskeleton

VEVD238

3,6,7

26,22,19

GVHD, DLE

[18*,100,101]

   

Calpain

   

Ki-67

Cell proliferation

(VCTD1481)

GB

167,148

SLE

[18*,51**]

Ku-70

DNA replication, repair

(ISSD79)

GB

?

SLE, PM/Scleroderma

[18*,51**]

La

Pol III transcription

(DEHD371),(DEHD374)

Not 1,2,3,8,9

45

SLE

[54]

  

LEED220

GB

?

 

[51**]

  

VQFQ358G

PV 3Cpro

50

 

[84]

Lamin A

Nuclear skeleton

VEID230

6

45

SLE-like Disease, APLA

[102,103]

Lamin B

Nuclear skeleton

(EEID448)

?

45,28

SLE-like Disease, APLA

[40,104]

  

(VEVD231)

    

Lamin C

Nuclear skeleton

VEID230

6

45

SLE-like Disease, APLA

[102,103]

Mi-2

DNA methylation,

VDPD1312

GB

75,72,48

DM

[51**]

 

chromatin remodeling

     

Nucleolin

Nucleolar RNA

?

?

16

SLE

[34,105]

 

binding protein

?

GA

88

 

[70]

NuMA

Mitosis

?

3,4,6,7,8

180,160

Sjögren's Syndrome

[40,106]

  

VATD1705

GB

175

 

[51**]

PARP

DNA binding protein

DEVD216

1,2,3,6

85,31

SLE

[40,107,108]

  

VDPD536

GB

M (89,72,62)

 

[69**]

PM-Scl

Exoribonuclease

(VEQD252)

GB

85,74

PM, Scleroderma

[18*,51**]

PMS1

DNA repair

ISAD496

GB

50,60

?

[51**]

PMS2

DNA repair

VEKD493

GB

60,50,36

?

[51**]

RNA helicase A

RNA processing, transcription

(DTPD96)

3

M (120-130)

SLE

[109]

RNA polymerase I

RNA synthesis

(ICPD448)

GB

?

Scleroderma

[18*,51**]

RNA polymerase II

RNA synthesis

(ITPD370)

GB

190,110,92

Scleroderma

[18*,51**]

SP1

Transcription

NSPD584

3,7

68,45,22

UCTD

[110]

SRP-72

Protein translation,

(SELD617)

3

66

DM/PM

[33]

 

ER localization

(VTPD573)

GB

62

 

[51**]

Topoisomerase I

DNA unwinding,

DDVD146 EEED170

3

M (76-82)

Scleroderma, PM

[40,49]

 

SR protein kinase

PEDD123

3

   
   

6

   
  

IEAD15

GB

98,75,72

 

[51**]

Topoisomerase II

DNA unwinding

?

?

M (125-160)

SLE, Fibrosing Alveolitis

[40]

Transglutaminase

Protein cross-linking

?

3

48

Coeliac Disease

[59,60]

UBF/NOR-90

Nucleolar transcription factor

?

?

M (24,32,35,55)

Sjögren's Syndrome,

[40]

  

(VRPD220)

GB

?

Scleroderma

[51**]

U1-70 kD

RNA splicing

DGPD341

3

40, 22

SLE, Scleroderma, MCTD

[38,96]

  

LGND409

GB

60

  

Vimentin

Cytoskeleton

IDVD259

1,2,3,8,12

44,36,25,15

SLE, BD, RA, Sjögren's Syndrome

[104,111,112,113]

  

DSVD85

    
  

?

HIV-1 protease

?

 

[85]

  1. The 'Cleavage site' column lists sites that have been definitively identified, either by mutational analysis of the substrate P1 aspartic acid residue, or by peptide sequencing of proteolytic fragments. Sequences in parentheses signify untested but likely cleavage sites. The fourth column lists proteases that have been implicated in the cleavage reaction. Caspases are listed by number. The substrate is susceptible to direct cleavage by the indicated recombinant caspase or by purified calpain or GB in an in vitro cleavage assay. The fifth column signifies molecular weights (in kDa) of cleavage products as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The acronyms used in this table (and not included in the abbreviations list at the start of the review) are listed in the appendix.
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Arthritis Research & Therapy

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