PMID- 36551517
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221225
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 14
IP  - 24
DP  - 2022 Dec 7
TI  - The Emerging Role of uORF-Encoded uPeptides and HLA uLigands in Cellular and 
      Tumor Biology.
LID - 10.3390/cancers14246031 [doi]
LID - 6031
AB  - Recent technological advances have facilitated the detection of numerous 
      non-canonical human peptides derived from regulatory regions of mRNAs, long 
      non-coding RNAs, and other cryptic transcripts. In this review, we first give an 
      overview of the classification of these novel peptides and summarize recent 
      improvements in their annotation and detection by ribosome profiling, mass 
      spectrometry, and individual experimental analysis. A large fraction of the novel 
      peptides originates from translation at upstream open reading frames (uORFs) that 
      are located within the transcript leader sequence of regular mRNA. In humans, 
      uORF-encoded peptides (uPeptides) have been detected in both healthy and 
      malignantly transformed cells and emerge as important regulators in cellular and 
      immunological pathways. In the second part of the review, we focus on various 
      functional implications of uPeptides. As uPeptides frequently act at the 
      transition of translational regulation and individual peptide function, we 
      describe the mechanistic modes of translational regulation through ribosome 
      stalling, the involvement in cellular programs through protein interaction and 
      complex formation, and their role within the human leukocyte antigen 
      (HLA)-associated immunopeptidome as HLA uLigands. We delineate how malignant 
      transformation may lead to the formation of novel uORFs, uPeptides, or HLA 
      uLigands and explain their potential implication in tumor biology. Ultimately, we 
      speculate on a potential use of uPeptides as peptide drugs and discuss how 
      uPeptides and HLA uLigands may facilitate translational inhibition of oncogenic 
      protein messages and immunotherapeutic approaches in cancer therapy.
FAU - Jurgens, Lara
AU  - Jurgens L
AUID- ORCID: 0000-0001-6910-8341
AD  - University Hospital Munster, Department of Medicine A, Hematology, Oncology, 
      Hemostaseology and Pneumology, 48149 Munster, Germany.
FAU - Wethmar, Klaus
AU  - Wethmar K
AUID- ORCID: 0000-0002-1899-3261
AD  - University Hospital Munster, Department of Medicine A, Hematology, Oncology, 
      Hemostaseology and Pneumology, 48149 Munster, Germany.
LA  - eng
GR  - 70113632/German Cancer Aid/
PT  - Journal Article
PT  - Review
DEP - 20221207
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9776223
OTO - NOTNLM
OT  - HLA uLigands
OT  - cancer
OT  - immunotherapy
OT  - non-canonical peptides
OT  - translation
OT  - uORFs
OT  - uPeptides
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/24 06:01
PMCR- 2022/12/07
CRDT- 2022/12/23 01:10
PHST- 2022/10/31 00:00 [received]
PHST- 2022/11/29 00:00 [revised]
PHST- 2022/11/30 00:00 [accepted]
PHST- 2022/12/23 01:10 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/24 06:01 [medline]
PHST- 2022/12/07 00:00 [pmc-release]
AID - cancers14246031 [pii]
AID - cancers-14-06031 [pii]
AID - 10.3390/cancers14246031 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Dec 7;14(24):6031. doi: 10.3390/cancers14246031.