An endogenous hybrid mRNA encodes TWE-PRIL, a functional cell surface TWEAK-APRIL fusion protein.
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.
Pradet-Balade
B
B
Department of Immunology and Oncology, Centro Nacional de Biotecnología, E-28049 Madrid, Spain.
Medema
J P
JP
López-Fraga
M
M
Lozano
J C
JC
Kolfschoten
G M
GM
Picard
A
A
Martínez-A
C
C
Garcia-Sanz
J A
JA
Hahne
M
M
D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D018920:Coculture Techniques; D000074049:Cytokine TWEAK; D004247:DNA; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors
C490341:ANP32B protein, human; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D000074049:Cytokine TWEAK; D009479:Neuropeptides; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors; D004247:DNA