ArticleJournal of cellular physiology2010
Progranulin (granulin/epithelin precursor) and its constituent granulin repeats repress transcription from cellular promoters.
Article in Journal of cellular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Charge and redox states modulate granulin-TDP-43 coacervation toward phase separation or aggregation.Biophysical journal · 2022Article
- Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia.PLoS pathogens · 2015Article
- A network of RNA and protein interactions in Fronto Temporal Dementia.Frontiers in molecular neuroscience · 2015Review
- Potential roles of microglial cell progranulin in HIV-associated CNS pathologies and neurocognitive impairment.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Review
- Low oxygen tension enhances hepatitis C virus replication.Journal of virology · 2013Article
- Mechanisms of granulin deficiency: lessons from cellular and animal models.Molecular neurobiology · 2013Review
- Insights into the role of progranulin in immunity, infection, and inflammation.Journal of leukocyte biology · 2013Review
- Progranulin: an emerging target for FTLD therapies.Brain research · 2012Review
- Cellular effects of progranulin in health and disease.Journal of molecular neuroscience : MN · 2011Review
- Structure, function, and mechanism of progranulin; the brain and beyond.Journal of molecular neuroscience : MN · 2011Review
- HIV-1 replication and latency are regulated by translational control of cyclin T1.Journal of molecular biology · 2011Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Progranulin (also known as granulin/epithelin precursor, GEP) is composed of seven granulin/epithelin repeats (granulins) and functions both as a full-length protein and as individual granulins. It is a secretory protein but a substantial amount of GEP is found inside cells, some in complexes with positive transcription elongation factor b (P-TEFb). GEP and certain granulins interact with the cyclin T1 subunit of P-TEFb, and with its HIV-1 Tat co-factor, leading to repression of transcription from the HIV promoter. We show that GEP lacking the signal peptide (GEPspm) remains inside cells and, like wild-type GEP, interacts with cyclin T1 and Tat. GEPspm represses transcription from the HIV-1 promoter at the RNA level. Granulins that bind cyclin T1 are phosphorylated by P-TEFb in vivo and in vitro on serine residues. GEPspm and those granulins that interact with cyclin T1 also inhibit transcription from cellular cad and c-myc promoters, which are highly dependent on P-TEFb, but not from the PCNA promoter. In addition, GEPspm and granulins repress transcriptional activation by VP16 or c-Myc, proteins that bind and recruit P-TEFb to responsive promoters. These data suggest that intracellular GEP is a promoter-specific transcriptional repressor that modulates the function of cellular and viral transcription factors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.