DCAF1 inhibits the NF-?B pathway by targeting p65.

DCAF1 is considered to be a general substrate-recognizing subunit of E3 ligases, it has been implicated to be directly involved in different cellular processes. DCAF1 is also defined as a constitutive binding partner of viral protein R (Vpr) of the human immunodeficiency virus type 1 (HIV-1) and is essential for ...
functions of Vpr. Here, we revealed that activation of NF-?B by virion-associated Vpr proteins highly depends on DCAF1, and that exogenous DCAF1 is capable of restraining NF-?B induction by external stimuli. Depletion of DCAF1 augments NF-?B activation. DCAF1 significantly inhibits the nuclear transportation of p65 through interactions with p65, after activation of the NF-?B pathway. Moreover, two main motifs of DCAF1 are identified to promote its inhibitory effects on the NF-?B pathway. Taken together, we propose a new role of DCAF1 in regulating cellular immune responses, beyond the function as a general adaptor for other cytokines or viral proteins.
Mesh Terms:
Carrier Proteins, Cytokines, HIV-1, Humans, NF-kappa B, Ubiquitin-Protein Ligases, vpr Gene Products, Human Immunodeficiency Virus
Immunol Lett
Date: Sep. 01, 2022
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