The PARP1-Siah1 Axis Controls HIV-1 Transcription and Expression of Siah1 Substrates
Graphical Abstract
Highlights
•PARP1 activity is required for optimal Tat activation of HIV-1 transcription
•PARP1 increases levels of ELL2 protein and ELL2-SEC, key for Tat-transactivation
•PARP1 and NCoR inhibit transcription of Siah1, an E3 ubiquitin ligase for ELL2
•PARP1 induces proteosomal degradation of Siah1 likely through a PARdU mechanism
Summary
Recent studies have revealed a key role of PARP1 that catalyzes the poly-ADP-ribosylation (PARylation) of substrates in regulating gene transcription. We show here that HIV-1 transcriptional activation also requires PARP1 activity. Because efficient HIV-1 transactivation is known to depend on the ELL2-containing super elongation complex (SEC), we investigated the functional relationship between PARP1 and ELL2-SEC in HIV-1 transcriptional control. We show that PARP1 elevates ELL2 protein levels to form more ELL2-SEC in cells. This effect is caused by PARP1’s suppression of expression of Siah1, an E3 ubiquitin ligasefor ELL2, at both mRNA and protein levels. At the mRNA level, PARP1 coordinates with the co-repressor NCoR to suppress Siah1 transcription. At the protein level, PARP1 promotes Siah1 proteolysis, likely through inducing PARylation-dependent ubiquitination (PARdU) of Siah1. Thus, a PARP1-Siah1 axis activates HIV-1 transcription and controls the expression of ELL2 and other Siah1 substrates.
- Tiberius's wife, Theodore's Mum, *Amory, died when Theo was born, due to birth complications (won't go into full detail in story, maybe only one or two mentions but read the warning at each chapter). Tom and Mattheo's Dad died when Mattheo was 2, Tom was 3, as he was killed by deatheaters. So when Theo and Mattheo were 13 and Tom 14, Tiberius and Maraia got together then 3 years later Rue was born.
The Black/Malfoy
Narcissa Black
Draco Malfoy - slytherin
- Narcissa kicked Lucius out years ago because he is a deatheater and she didn't want her child to grow up like she did.
The Berkshires and Zabini
*Claire Berkshire
*Charles Berkshire
Lorenzo Berkshire - slytherin
Juniper Berkshire - Ravenclaw
Blaise Zabini - slytherin
Blaise lives with the Berkshires because his Mum is rarely there and only shows up every few months and he doesn't know who his Dad is.
The Primswoods
*Martha Primswood
*Lionel Primswood
*Dylan Primswood - slytherin
*Xander Primswood - hufflepuff
OTHER CHARACTERS all the Weasleys, Hermione etc. other OC's
We're so happy to introduce our bright and beautiful team of artists, writers and mods!
Together, we're hoping to create a zine dedicated to the relationship between Jung Hoseok and Kim Taehyung of BTS. The zine will be available physcially and digitally, with the hope that we can raise money for a nominated charity.