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Prelamin A interacts with RIPK1 in ZMPSTE24-deficient cells

ABSTRACT: To understand the gain-of-toxicity of unprocessed prelamin A, we sought to identify the specific binding proteins of prelamin A that do not interact with mature lamin A. Because prelamin A is specifically localized to the nuclear envelope, we used ascorbate peroxidase 2 (APEX2)-based proximity labelling combined with mass spectrometry, which allows for temporally and spatially resolved proteomic mapping, to isolate the specific binding proteins of prelamin A.

ORGANISM(S): Homo Sapiens

SUBMITTER: Daichao Xu

PROVIDER: PXD049033 | iProX | Wed Jan 31 00:00:00 GMT 2024

REPOSITORIES: iProX

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Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1.

Yang Yuanxin Y Zhang Jian J Lv Mingming M Cui Na N Shan Bing B Sun Qi Q Yan Lingjie L Zhang Mengmeng M Zou Chengyu C Yuan Junying J Xu Daichao D

Nature cell biology 20240327 4

Defects in the prelamin A processing enzyme caused by loss-of-function mutations in the ZMPSTE24 gene are responsible for a spectrum of progeroid disorders characterized by the accumulation of farnesylated prelamin A. Here we report that defective prelamin A processing triggers nuclear RIPK1-dependent signalling that leads to necroptosis and inflammation. We show that accumulated prelamin A recruits RIPK1 to the nucleus to facilitate its activation upon tumour necrosis factor stimulation in ZMPS ...[more]

PMID: 38538837

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