1. hTERT cell line 에 PAH 노출 후 molecular study (cell count, Viability, Copy number variation 등 )

2. Leukemia cell line - THP-1 cell line 에서 발굴된 Protein (Prelamin-A/C, Poly [ADP-

ribose] polymerase 1) 의 mRNA 수준에서 expression study - Western blotting 을 이용한 prelamin-A/C, poly [ADP-ribose]

polymerase 1 Protein 분석3. In vivo Zebrafish model - Western blotting 을 이용한 LMNA, PARP-1 Protein 분석 - Protein (Prelamin-A/C(LMNA), Poly [ADP-ribose] polymerase

1 (PARP-1)) 의 mRNA 수준에서 expression study

4. SETBP1 mutation in MDS/MPN Patients

실험계획

PAHs Protein Fold change

Benzopyrene annexin A1 13.38prelamin-A/C isoform 3 10.04NADPH:adrenodoxin oxidoreductase, mitochondrial isoform 2 precursor 5.3squalene synthase 5.3heterogeneous nuclear ribonucleoproteins A2/B1 isoform B1 4.82T-complex protein 1 subunit theta 4.35talin-1 4.35

Pentacene prelamin-A/C isoform 3 6.9DNA topoisomerase 2-alpha 6.38annexin A1 6.38poly [ADP-ribose] polymerase 1 5.85squalene synthase 5.33talin-1 5.33PREDICTED: u5 small nuclear ribonucleoprotein 200 kDa helicase-like, partial 4.81

Fluoranthene poly [ADP-ribose] polymerase 1 6.21elongation factor 1-gamma 5.21heat shock 70 kDa protein 1A/1B 5.21heterogeneous nuclear ribonucleoproteins A2/B1 isoform B1 5.21probable ATP-dependent RNA helicase DDX5 5.21T-complex protein 1 subunit theta 5.21

Pyrene talin-1 16.82DNA topoisomerase 2-alpha 8.17filamin-C isoform b 7.16E3 SUMO-protein ligase RanBP2 5.65CAD protein 5.14　 poly [ADP-ribose] polymerase 1 5.14

No. Accession Reference MW Fold.change

1 62414289 vimentin [Homo sapiens]53619.1

7 19.39

2 27436948 prelamin-A/C isoform 370618.1

6 10.04 3 4502101 annexin A1 38690 13.38

4 29553970 histone H2A.J [Homo sapiens]14010.9

3 5.84

5 21166389 histone H2B type 1-C/E/F/G/I [Homo sapiens]13897.5

6 5.14

6 223029410 talin-1269596.

3 4.35

7 48762932 T-complex protein 1 subunit theta 59582.6

1 4.35

8 67089147 squalene synthase48084.2

6 5.30

9 111118983 NADPH:adrenodoxin oxidoreductase, mitochondrial isoform 2 precursor 54444.4

7 5.30

10 14043072 heterogeneous nuclear ribonucleoproteins A2/B1 isoform B1 37406.6

9 4.82 11 4503481 elongation factor 1-gamma 50087.2 5.30

12 156151396 heterogeneous nuclear ribonucleoprotein R isoform 359915.8

4 4.35

Vimentin plays a significant role in supporting and anchoring the position of the organelles in the cytosol. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either lat-erally or terminally.

vimentin

talin-1

Talin-1 is a protein that in humans is encoded by the TLN1 gene.This gene encodes a cytoskeletal protein which is concentrated in ar-eas of cell-substratum and cell-cell contacts. This protein plays a signif -icant role in the assembly of actin filaments and in spreading and mi-gration of various cell types, including fibroblasts and osteoclasts.

SETBP1 mutations in MDS/MPN

Nature Genet-ics

Nature Genet-ics

No. 등록번호 이름 진단명1 18681799 김병조 Atypical CML

2 71148645 김천석3 70769053 박봉심4 70891553 박정희5 70487425 이나리6 16515403 이영옥7 06108625 이재필8 70370093 임점순9 16748652 조광일

10 70891943 조규완11 12166963 김춘자 CMML

12 06465527 한일국13 14328118 박연님14 13936755 하숙자15 06019541 이병기16 70313562 박종금17 70710289 박병동18 11891461 김병옥19 70944733 박종우20 17580835 조규윤21 14832752 정암일22 70147274 고재선23 18998223 김영식24 18922803 양행묵25 18951919 김근호26 19728716 정우진 JMML

27 70796465 민지인28 19995606 박시후29 19090444 김택종 MDS MPN

30 07837331 김재길

Tumor type Number of samplesMDS/MPN Atypical CML 10 CMML 15 JMML 3 MDS/MPN 2Total 30

M 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

M 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

607bp

54hpf Normal 0.57507DMSO 0.60105400nM 0.77247600nM 0.65929800nM 0.93061

　 1μM 1.9846

54hpf

zebrafish mtDNA cytochrome b gene and β-actin

78hpf Normal 1.23676DMSO 1.0657400nM 0.77141600nM 0.88588

　 800nM 2.01882

78hpf

54hpf

78hpf

54hpf 78hpf