Zhangfei, a novel regulator of the human nerve growth factor receptor, trkA.
The replication of herpes simplex virus (HSV) in epithelial cells, and during reactivation from latency in sensory neurons, depends on a ubiquitous cellular protein called host cell factor (HCF). The HSV transactivator, VP16, which initiates the viral replicative cycle, binds HCF as do some other cellular proteins. Of these, the neuronal transcription factor Zhangfei suppresses the ability of VP16 to initiate the replicative cycle. It also suppresses Luman, another cellular transcription factor that binds HCF. Interactions of nerve growth factor (NGF) and its receptor tropomyosin-related kinase (trkA) appear to be critical for maintaining HSV latency. Because the neuronal transcription factor Brn3a, which regulates trkA expression, has a motif for binding HCF, we investigated if Zhangfei had an effect on its activity. We found that Brn3a required HCF for activating the trkA promoter and Zhangfei suppressed its activity in non-neuronal cells. However, in neuron-like NGF-differentiated PC12 cells, both Brn3a and Zhangfei activated the trkA promoter and induced the expression of endogenous trkA. In addition, capsaicin, a stressor, which activates HSV in in vitro models of latency, decreased levels of Zhangfei and trkA transcripts in NGF-differentiated PC12 cells.
Valderrama
Ximena
X
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Rapin
Noreen
N
Misra
Vikram
V
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1 / Q000378:metabolism*; D006801:Humans; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016716:PC12 Cells / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000187:drug effects; D014709:Vero Cells
D050976:Basic-Leucine Zipper Transcription Factors; C411104:CREBZF protein, human; D051863:Host Cell Factor C1; D009419:Nerve Tissue Proteins; D011506:Proteins; D015534:Trans-Activators; D050819:Transcription Factor Brn-3A; D020932:Nerve Growth Factor; D011494:Protein Kinases; D020917:Receptor, trkA; C530988:tropomyosin-related kinase-B, bovine