2. Academic Validation
  3. pLxIS-containing domains are biochemically flexible regulators of interferons and metabolism

pLxIS-containing domains are biochemically flexible regulators of interferons and metabolism

  • Mol Cell. 2024 Jul 11;84(13):2436-2454.e10. doi: 10.1016/j.molcel.2024.05.030.
Lauren M Landau 1,  Neha Chaudhary 2,  Yun Chen Tien 2,  Magdalena Rogozinska 2,  Shakchhi Joshi 3,  Conghui Yao 3,  Joseph Crowley 3,  Karthik Hullahalli 4,  Ian W Campbell 4,  Matthew K Waldor 4,  Marcia Haigis 3,  Jonathan C Kagan 5
Affiliations

Affiliations

  • 1 Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
  • 2 Cambridge Research Center, AbbVie, Inc., Cambridge, MA, USA.
  • 3 Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • 4 Division of Infectious Diseases, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • 5 Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: jonathan.kagan@childrens.harvard.edu.
PMID: 38925114 DOI: 10.1016/j.molcel.2024.05.030
Abstract

Signal transduction proteins containing a pLxIS motif induce interferon (IFN) responses central to Antiviral immunity. Apart from their established roles in activating the IFN regulator factor (IRF) transcription factors, the existence of additional pathways and functions associated with the pLxIS motif is unknown. Using a synthetic biology-based platform, we identified two orphan pLxIS-containing proteins that stimulate IFN responses independent of all known pattern-recognition receptor pathways. We further uncovered a diversity of pLxIS signaling mechanisms, where the pLxIS motif represents one component of a multi-motif signaling entity, which has variable functions in activating IRF3, the TRAF6 ubiquitin Ligase, IκB kinases, mitogen-activated protein kinases, and metabolic activities. The most diverse pLxIS signaling mechanisms were associated with the highest Antiviral activities in human cells. The flexibility of domains that regulate IFN signaling may explain their prevalence in nature.

Keywords

GMIP; IRSp53; MAVS; MyD88; STING; TASL; TBK1; TRAF6; TRIF; infection; interferon; macrophages; synthetic biology.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z