The C-mer gene is induced by Epstein-Barr virus immediate-early protein BRLF1.
BRLF1 (R) is one of two Epstein-Barr virus (EBV) immediate-early proteins that mediate the switch from the latent to the lytic form of viral replication. In this report, we show that R induces expression of the cellular C-mer gene in a variety of cell lines. C-mer expression was detected in lymphoblastoid cells immortalized with wild-type EBV but not in lymphoblastoid cells immortalized with an EBV that had BRLF1 deleted. Oral hairy leukoplakia tongue tissue, which contains the lytic form of EBV replication, also has enhanced C-mer expression. C-mer is a receptor tyrosine kinase activated by the ligand Gas6. C-mer is required for phagocytosis of apoptotic debris by monocytes/macrophages and retinal pigment epithelial cells and is capable of producing an antiapoptotic signal. Modulation of the C-mer signal transduction cascade by a variety of different approaches did not alter the ability of R to induce lytic EBV gene transcription. Therefore, C-mer activation may be important for some other aspect of lytic EBV infection.
UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, NC 27599-7295, USA.
Yuling
Y
Li
Nupam P
NP
Mahajan
Jennifer
J
Webster-Cyriaque
Prasanna
P
Bhende
Gregory K
GK
Hong
H Shelton
HS
Earp
Shannon
S
Kenney
D002051:Burkitt Lymphoma / Q000821:virology; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D015534:Trans-Activators / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014764:Viral Proteins; D000076202:c-Mer Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D000076202:c-Mer Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C068382:BRLF1 protein, Human herpesvirus 4; C097072:MERTK protein, human