The UBE2F-CRL5ASB11-DIRAS2 axis is an oncogene and tumor suppressor cascade in pancreatic cancer cells.
UBE2F, a neddylation E2, neddylates CUL5 to activate cullin-RING ligase-5, upon coupling with neddylation E3 RBX2/SAG. Whether and how UBE2F controls pancreatic tumorigenesis is previously unknown. Here, we showed that UBE2F is essential for the growth of human pancreatic cancer cells with KRAS mutation. In the mouse KrasG12D pancreatic ductal adenocarcinoma (PDAC) model, Ube2f deletion suppresses cerulein-induced pancreatitis, and progression of acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia. Mechanistically, Ube2f deletion inactivates the Mapk-c-Myc signals via blocking ubiquitylation of Diras2, a substrate of CRL5Asb11 E3 ligase. Biologically, DIRAS2 suppresses growth and survival of human pancreatic cancer cells harboring mutant KRAS, and Diras2 deletion largely rescues the phenotypes induced by Ube2f deletion. Collectively, Ube2f or Diras2 plays a tumor-promoting or tumor-suppressive role in the mouse KrasG12D PDAC model, respectively. The UBE2F-CRL5ASB11 axis could serve as a valid target for pancreatic cancer, whereas the levels of UBE2F or DIRAS2 may serve as prognostic biomarkers for PDAC patients.
Pubmed ID: 38574733 RIS Download
Research resources used in this publication
- C57BL/6JGpt-Diras2em1Cflox/Gpt (RRID:IMSR_GPT:T026188) (organism)
- PANC-1 (RRID:CVCL_0480) (cell line)
- B6.129S4-Krastm4Tyj/J (RRID:IMSR_JAX:008179) (organism)
- STOCK Ptf1atm1(cre)Hnak/RschJ (RRID:IMSR_JAX:023329) (organism)
- MIA PaCa-2 (RRID:CVCL_0428) (cell line)
- HEK293 (RRID:CVCL_0045) (cell line)
- BxPC-3 (RRID:CVCL_0186) (cell line)
Additional research tools detected in this publication
None foundAntibodies used in this publication
- Anti-FLAG® M2 Magnetic Beads (RRID:AB_2637089)
- Brilliant Violet 421(TM) anti-mouse Ly-6G (RRID:AB_10897944)
- APC anti-mouse F4/80 (RRID:AB_893481)
- FITC anti-mouse/human CD11b (RRID:AB_312788)
- Brilliant Violet 605(TM) anti-mouse CD45 (RRID:AB_2650656)
- Mouse Anti-Human UBC12 Monoclonal Antibody, Unconjugated, Clone L-34 (RRID:AB_2211030)
- UBE2F antibody (RRID:AB_2210295)
- Sox9 (D8G8H) Rabbit mAb #82630 (RRID:AB_2665492)
- RNF7 antibody (RRID:AB_10697836)
- Rbx1 Antibody (E-11) (RRID:AB_2722527)
- Ras antibody [EP1125Y] (RRID:AB_2121042)
- Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (RRID:AB_2315049)
- Rabbit Normal igg Control antibody, Unconjugated (RRID:AB_145841)
- Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (20G11) Rabbit mAb (RRID:AB_331772)
- p44/42 MAPK (Erk1/2) (3A7) Mouse mAb (RRID:AB_10695739)
- Mucin 5AC antibody [45M1] (RRID:AB_2146844)
- Recombinant Anti-Ki67 antibody [SP6] (RRID:AB_302459)
- ANTI-FLAG(R) antibody produced in rabbit (RRID:AB_439687)
- Normal Mouse IgG (RRID:AB_145840)
- Monoclonal ANTI-FLAG® M2 antibody produced in mouse (RRID:AB_262044)
- DIRAS2 antibody (RRID:AB_2261563)
- Anti-Cullin 5/CUL-5 antibody (RRID:AB_3073511)
- IQGAP1 (C-9) (RRID:AB_10988556)
- CUL1 antibody (RRID:AB_2086291)
- c-Myc (D84C12) XP Rabbit mAb (RRID:AB_1903938)
- B-Raf (E3T5C) Mouse mAb (RRID:AB_2943238)
- Mouse Anti-Human ASB11 Polyclonal Antibody, Unconjugated (RRID:AB_463492)
- Rabbit Anti-Human HA Antibody, Unconjugated (RRID:AB_260070)
- Anti-Beta Actin Antibody (RRID:AB_3073201)
- APOBEC3B (E9A2G) Rabbit mAb (RRID:AB_2799203)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
Anti-FLAG® M2 Magnetic Beads (antibody)
RRID:AB_2637089
This monoclonal targets FLAG
View all literature mentionsBrilliant Violet 421(TM) anti-mouse Ly-6G (antibody)
RRID:AB_10897944
This monoclonal targets Ly-6G
View all literature mentionsAPC anti-mouse F4/80 (antibody)
RRID:AB_893481
This monoclonal targets F4/80
View all literature mentionsFITC anti-mouse/human CD11b (antibody)
RRID:AB_312788
This monoclonal targets CD11b
View all literature mentionsBrilliant Violet 605(TM) anti-mouse CD45 (antibody)
RRID:AB_2650656
This monoclonal targets CD45
View all literature mentionsMouse Anti-Human UBC12 Monoclonal Antibody, Unconjugated, Clone L-34 (antibody)
RRID:AB_2211030
This monoclonal targets UBE2M
View all literature mentionsUBE2F antibody (antibody)
RRID:AB_2210295
This polyclonal targets UBE2F
View all literature mentionsSox9 (D8G8H) Rabbit mAb #82630 (antibody)
RRID:AB_2665492
This monoclonal targets Sox9
View all literature mentionsRbx1 Antibody (E-11) (antibody)
RRID:AB_2722527
This monoclonal targets Rbx1
View all literature mentionsRas antibody [EP1125Y] (antibody)
RRID:AB_2121042
This monoclonal targets Hras1
View all literature mentionsPhospho-Akt (Ser473) (D9E) XP® Rabbit mAb (antibody)
RRID:AB_2315049
This monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsRabbit Normal igg Control antibody, Unconjugated (antibody)
RRID:AB_145841
This unknown targets Rabbit Normal igg Control antibody
View all literature mentionsPhospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204) (20G11) Rabbit mAb (antibody)
RRID:AB_331772
This monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsp44/42 MAPK (Erk1/2) (3A7) Mouse mAb (antibody)
RRID:AB_10695739
This monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsMucin 5AC antibody [45M1] (antibody)
RRID:AB_2146844
This monoclonal targets MUC5AC
View all literature mentionsRecombinant Anti-Ki67 antibody [SP6] (antibody)
RRID:AB_302459
This recombinant monoclonal targets Ki67
View all literature mentionsANTI-FLAG(R) antibody produced in rabbit (antibody)
RRID:AB_439687
This polyclonal targets FLAG
View all literature mentionsNormal Mouse IgG (antibody)
RRID:AB_145840
This polyclonal secondary targets not applicable
View all literature mentionsMonoclonal ANTI-FLAG® M2 antibody produced in mouse (antibody)
RRID:AB_262044
This monoclonal targets FLAG
View all literature mentionsDIRAS2 antibody (antibody)
RRID:AB_2261563
This polyclonal targets DIRAS2
View all literature mentionsAnti-Cullin 5/CUL-5 antibody (antibody)
RRID:AB_3073511
This polyclonal targets Cullin 5/CUL-5
View all literature mentionsIQGAP1 (C-9) (antibody)
RRID:AB_10988556
This monoclonal targets IQGAP1 (C-9)
View all literature mentionsc-Myc (D84C12) XP Rabbit mAb (antibody)
RRID:AB_1903938
This monoclonal targets c-Myc (D84C12) XP Rabbit mAb
View all literature mentionsB-Raf (E3T5C) Mouse mAb (antibody)
RRID:AB_2943238
This monoclonal targets BRAF
View all literature mentionsMouse Anti-Human ASB11 Polyclonal Antibody, Unconjugated (antibody)
RRID:AB_463492
This polyclonal targets Human ASB11
View all literature mentionsRabbit Anti-Human HA Antibody, Unconjugated (antibody)
RRID:AB_260070
This unknown targets HA
View all literature mentionsAnti-Beta Actin Antibody (antibody)
RRID:AB_3073201
This polyclonal targets Beta Actin
View all literature mentionsAPOBEC3B (E9A2G) Rabbit mAb (antibody)
RRID:AB_2799203
This monoclonal targets APOBEC3B
View all literature mentionsC57BL/6JGpt-Diras2em1Cflox/Gpt (organism)
RRID:IMSR_GPT:T026188
Mus musculus with name C57BL/6JGpt-Diras2em1Cflox/Gpt from IMSR.
View all literature mentionsPANC-1 (cell line)
RRID:CVCL_0480
Cell line PANC-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsB6.129S4-Krastm4Tyj/J (organism)
RRID:IMSR_JAX:008179
Mus musculus with name B6.129S4-Krastm4Tyj/J from IMSR.
View all literature mentionsSTOCK Ptf1atm1(cre)Hnak/RschJ (organism)
RRID:IMSR_JAX:023329
Mus musculus with name STOCK Ptf1atm1(cre)Hnak/RschJ from IMSR.
View all literature mentionsMIA PaCa-2 (cell line)
RRID:CVCL_0428
Cell line MIA PaCa-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsHEK293 (cell line)
RRID:CVCL_0045
Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsBxPC-3 (cell line)
RRID:CVCL_0186
Cell line BxPC-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions
