Adenovirus E3-6.7K protein is required in conjunction with the E3-RID protein complex for the internalization and degradation of TRAIL receptor 2.
Adenoviruses (Ads) encode several proteins within the early region 3 (E3) transcription unit that help protect infected cells from elimination by the immune system. Among these immunomodulatory proteins, the receptor internalization and degradation (RID) protein complex, which is composed of the RIDalpha (formerly E3-10.4K) and RIDbeta (formerly E3-14.5K) subunits, stimulates the internalization and degradation of certain members of the tumor necrosis factor (TNF) receptor superfamily, thus blocking apoptosis initiated by Fas and TNF-related apoptosis-inducing ligand (TRAIL). The experiments reported here show that TRAIL receptor 2 (TR2) is cleared from the cell surface in Ad-infected cells. Virus mutants containing deletions that span E3 were used to show that the RID and E3-6.7K proteins are both necessary for the internalization and degradation of TR2, whereas only the RID protein is required for TRAIL receptor 1 downregulation. In addition, replication-defective Ad vectors that express individual E3 proteins were used to establish that the RID and E3-6.7K proteins are sufficient to clear TR2. These data demonstrate that E3-6.7K is an important component of the antiapoptosis arsenal encoded by the E3 transcription unit of subgroup C Ads.
Lichtenstein
Drew L
DL
Department of Molecular Microbiology and Immunology, School of Medicine, Saint Louis University, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
Doronin
Konstantin
K
Toth
Karoly
K
Kuppuswamy
Mohan
M
Wold
William S M
WS
Tollefson
Ann E
AE
D017503:Adenovirus E3 Proteins / Q000502:physiology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D011506:Proteins / Q000502:physiology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*
D017503:Adenovirus E3 Proteins; D011506:Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases