PMID- 29780898
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2415-1289 (Print)
IS  - 2415-1289 (Electronic)
IS  - 2415-1289 (Linking)
VI  - 3
DP  - 2018
TI  - SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma.
PG  - 20
LID - 10.21037/tgh.2018.04.04 [doi]
LID - 20
AB  - Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs 
      predominantly in patients with underlying chronic liver disease and cirrhosis. 
      The large spectrum of protein post-translational modification (PTM) includes 
      numerous critical signaling events that occur during neoplastic transformation. 
      PTMs occur to nearly all proteins and increase the functional diversity of 
      proteins. We have reviewed the role of two major PTMs, SUMOylation and 
      phosphorylation, in the altered signaling of key players in HCC. SUMOylation is a 
      PTM that involves addition of a small ubiquitin-like modifiers (SUMO) group to 
      proteins. It is known to regulate protein stability, protein-protein 
      interactions, trafficking and transcriptional activity. The major pathways that 
      are regulated by SUMOylation and may influence HCC are regulation of 
      transcription, cell growth pathways associated with B-cell lymphoma 2 (Bcl-2) and 
      methionine adenosyltransferases (MAT), oxidative stress pathways [nuclear 
      erythroid 2-related factor 2 (Nrf2)], tumor suppressor pathways (p53), 
      hypoxia-inducible signaling [hypoxia-inducible factor-1 (HIF-1)], glucose and 
      lipid metabolism, nuclear factor kappa B (NF-kappaB) and beta-Catenin signaling. 
      Phosphorylation is an extensively studied PTM in HCC. The mitogen-activated 
      protein kinase (MAPK), phosphatidyl inositol/AK-strain transforming (PI3K/AKT), 
      and C-SRC pathways have been extensively studied for deregulation of kinases and 
      alteration in signaling of targets through phosphorylation of their substrates. 
      Cross-talk between phosphorylation and SUMOylation is known to influence 
      transcriptional activity of proteins and protein-protein interactions. In HCC, 
      several SUMOylation-dependent phosphorylation events have been studied such as 
      MAPK activation and c-SRC activity that have been reviewed in this work. The 
      drastic effects of site-specific phosphorylation or SUMOylation on enzyme 
      activity of signaling players and its effect on growth and tumorigenesis suggests 
      that these PTMs are novel targets for therapeutic intervention in HCC.
FAU - Tomasi, Maria Lauda
AU  - Tomasi ML
AD  - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
FAU - Ramani, Komal
AU  - Ramani K
AD  - Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
LA  - eng
GR  - K01 AA022372/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20180423
PL  - China
TA  - Transl Gastroenterol Hepatol
JT  - Translational gastroenterology and hepatology
JID - 101683450
PMC - PMC5945704
OTO - NOTNLM
OT  - Hepatocellular carcinoma (HCC)
OT  - SUMOylation
OT  - phosphorylation
OT  - post-translational modification
COIS- Conflicts of Interest: The authors have no conflicts of interest to declare.
EDAT- 2018/05/22 06:00
MHDA- 2018/05/22 06:01
PMCR- 2018/04/23
CRDT- 2018/05/22 06:00
PHST- 2018/03/16 00:00 [received]
PHST- 2018/04/11 00:00 [accepted]
PHST- 2018/05/22 06:00 [entrez]
PHST- 2018/05/22 06:00 [pubmed]
PHST- 2018/05/22 06:01 [medline]
PHST- 2018/04/23 00:00 [pmc-release]
AID - tgh-03-2018.04.04 [pii]
AID - 10.21037/tgh.2018.04.04 [doi]
PST - epublish
SO  - Transl Gastroenterol Hepatol. 2018 Apr 23;3:20. doi: 10.21037/tgh.2018.04.04. 
      eCollection 2018.