PMID- 25946643
OWN - NLM
STAT- MEDLINE
DCOM- 20160421
LR  - 20200930
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 14
IP  - 14
DP  - 2015
TI  - Ras transformation results in cleavage of reticulon protein Nogo-B that is 
      associated with impairment of IFN response.
PG  - 2301-10
LID - 10.1080/15384101.2015.1044187 [doi]
AB  - Dysregulation of Ras signaling is the major cause of various cancers. Aberrant 
      Ras signaling, however, provides a favorable environment for many viruses, making 
      them suitable candidates as cancer-killing therapeutic agents. Susceptibility of 
      cancer cells to such viruses is mainly due to impaired type I interferon (IFN) 
      response, often as a result of activated Ras/ERK signaling in these cells. In 
      this study, we searched for cellular factors modulated by Ras signaling and their 
      potential involvement in promoting viral oncolysis. We found that upon Ras 
      transformation of NIH-3T3 cells, the N-terminus of Nogo-B (reticulon 4) was 
      proteolytically cleaved. Interestingly, Nogo knockdown (KD) in non-transformed 
      and Ras-transformed cells both enhanced virus-induced IFN response, suggesting 
      that both cleaved and uncleaved Nogo can suppress IFN response. However, 
      pharmacological blockade of Nogo cleavage in Ras-transformed cells significantly 
      enhanced virus-induced IFN response, suggesting that cleaved Nogo contributes to 
      enhanced IFN suppression in these cells. We further showed that IFN suppression 
      associated with Ras-induced Nogo-B cleavage was distinct from but synergistic 
      with that associated with an activated Ras/ERK pathway. Our study therefore 
      reveals an important and novel role of Nogo-B and its cleavage in the suppression 
      of anti-viral immune responses by oncogenic Ras transformation.
FAU - Ahn, Dae-Gyun
AU  - Ahn DG
AD  - a Department of Microbiology and Immunology ; Dalhousie University ; Halifax , 
      Nova Scotia , Canada.
FAU - Sharif, Tanveer
AU  - Sharif T
FAU - Chisholm, Kenneth
AU  - Chisholm K
FAU - Pinto, Devanand M
AU  - Pinto DM
FAU - Gujar, Shashi A
AU  - Gujar SA
FAU - Lee, Patrick W K
AU  - Lee PW
LA  - eng
GR  - 137152/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150506
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Nogo-B receptor, mouse)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Cell Surface)
RN  - 9008-11-1 (Interferons)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
CIN - Cell Cycle. 2015 Aug 3;14(15):2392-3. PMID: 26103007
MH  - Amino Acid Sequence
MH  - Animals
MH  - HEK293 Cells
MH  - Humans
MH  - Interferons/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - NIH 3T3 Cells
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Cell Surface/antagonists & inhibitors/genetics/*metabolism
MH  - ras Proteins/genetics/*metabolism
PMC - PMC4614670
OTO - NOTNLM
OT  - Nogo
OT  - cleavage
OT  - interferon
OT  - reticulon 4B
OT  - transformed cells
EDAT- 2015/05/07 06:00
MHDA- 2016/04/22 06:00
PMCR- 2016/05/06
CRDT- 2015/05/07 06:00
PHST- 2015/05/07 06:00 [entrez]
PHST- 2015/05/07 06:00 [pubmed]
PHST- 2016/04/22 06:00 [medline]
PHST- 2016/05/06 00:00 [pmc-release]
AID - 1044187 [pii]
AID - 10.1080/15384101.2015.1044187 [doi]
PST - ppublish
SO  - Cell Cycle. 2015;14(14):2301-10. doi: 10.1080/15384101.2015.1044187. Epub 2015 
      May 6.