An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein

EMBO J. 2002 Nov 1;21(21):5711-20. doi: 10.1093/emboj/cdf565.


TWEAK and APRIL are two recently identified tumour necrosis factor (TNF) ligand family members, implicated in angiogenesis and immune regulation, respectively. TWEAK is a transmembrane protein expressed on the cell surface, whereas APRIL acts solely as a secreted factor. In this report, using RACE, RT-PCR, cDNA library screening and an RNase protection assay, we characterize a hybrid transcript between TWEAK and APRIL mRNAs. The encoded TWE-PRIL protein is composed of TWEAK cytoplasmic and transmembrane domains fused to the APRIL C-terminal domain. TWE-PRIL mRNA is expressed and translated in human primary T cells and monocytes, and endogenous TWE-PRIL protein was detected in primary human T lymphocytes and monocytic cell lines. TWE-PRIL is membrane anchored and presents the APRIL receptor-binding domain at the cell surface. It is a biologically active ligand, as it stimulates cycling in T- and B-lymphoma cell lines. Much like membrane-bound and secreted TNF-alpha, the different cellular localizations of TWE-PRIL and APRIL suggest that they exert distinct biological roles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Carrier Proteins / genetics*
  • Cell Line
  • Coculture Techniques
  • Cytokine TWEAK
  • DNA
  • Humans
  • Molecular Sequence Data
  • Monocytes / metabolism
  • Neuropeptides / genetics*
  • Nuclear Proteins / genetics*
  • RNA, Messenger / genetics*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • Tumor Necrosis Factors


  • ANP32B protein, human
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Cytokine TWEAK
  • Neuropeptides
  • Nuclear Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • TNFSF12 protein, human
  • Tumor Necrosis Factors
  • DNA