Dataset Information

Interferon-Induced PARP14-Mediated ADP-Ribosylation in p62 Bodies Requires an Active Ubiquitin-Proteasome System

ABSTRACT: Biomolecular condensates are cellular compartments without enveloping membranes, enabling them to dynamically adjust their composition in response to environmental changes through post-translational modifications. A recent study has revealed that interferon-induced ADP-ribosylation (ADPr), which can be reversed by a SARS-CoV-2-encoded hydrolase, is enriched within a condensate. However, the identity of the condensate and responsible host ADP-ribosyltransferase remain elusive. Here, we demonstrate that interferon induces ADPr through transcriptional activation of PARP14, requiring both its physical presence and catalytic activity for condensate formation. Interferon-induced ADPr colocalizes with PARP14 and its protein-level regulator DTX3L, and these PARP14/ADPr condensates contain key components of p62 bodies—including the selective autophagy receptor p62 and its binding partners NBR1 and TAX1BP1, along with K48-linked and K63-linked polyubiquitin chains—but lack the autophagosome marker LC3B. Knockdown of p62 disrupts the formation of these ADPr condensates. Importantly, these structures are unaffected by autophagy inhibition but depend on ubiquitin-activating enzyme E1, E3 ligase DTX3L, and proteasome activity. Taken together, these findings demonstrate that interferon triggers PARP14-mediated ADP-ribosylation in p62 bodies, which requires an active ubiquitin-proteasome system.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Ivo Hendriks

LAB HEAD: Ivo Hendriks

PROVIDER: PXD057944 | Pride | 2025-05-26

REPOSITORIES: Pride

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			Action	DRS
	20240917_AST0_NEO4_SCL-IAH_collab_AKLL_IP_DIA_C_C_01.raw	Raw
	20240917_AST0_NEO4_SCL-IAH_collab_AKLL_IP_DIA_C_C_02.raw	Raw
	20240917_AST0_NEO4_SCL-IAH_collab_AKLL_IP_DIA_C_C_03.raw	Raw
	20240917_AST0_NEO4_SCL-IAH_collab_AKLL_IP_DIA_C_C_04.raw	Raw
	20240917_AST0_NEO4_SCL-IAH_collab_AKLL_IP_DIA_C_P62_01.raw	Raw

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Interferon-induced PARP14-mediated ADP-ribosylation in p62 bodies requires the ubiquitin-proteasome system.

Raja Rameez R Biswas Banhi B Abraham Rachy R Wang Yiran Y Chang Che-Yuan CY Hendriks Ivo A IA Buch-Larsen Sara C SC Liu Hongrui H Yang Xingyi X Wang Chenyao C Vu Hien H Hamacher-Brady Anne A Cai Danfeng D Leung Anthony K L AKL

The EMBO journal 20250407 10

Biomolecular condensates are cellular compartments without enveloping membranes, enabling them to dynamically adjust their composition in response to environmental changes through post-translational modifications. Recent work has revealed that interferon-induced ADP-ribosylation (ADPr), which can be reversed by a SARS-CoV-2-encoded hydrolase, is enriched within a condensate. However, the identity of the condensate and the responsible host ADP-ribosyltransferase remain elusive. Here, we demonstra ...[more]

PMID: 40195501

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