Different Prelamin A Forms Accumulate in Human Fibroblasts: a Study in Experimental Models and Progeria

Overview

Journal Eur J Histochem

Specialty Biochemistry

Date 2018 Sep 27

PMID 30256865

Citations 1

Authors

S Dominici

V Fiori

M Magnani

E Schena

C Capanni

D Camozzi

M R DApice

C Le Dour

M Auclair

M Caron

G Novelli

C Vigouroux

N M Maraldi

G Lattanzi

Affiliations

Soon will be listed here.

Abstract

Lamin A is a component of the nuclear lamina mutated in a group of human inherited disorders known as laminopathies. Among laminopathies, progeroid syndromes and lipodystrophies feature accumulation of prelamin A, the precursor protein which, in normal cells, undergoes a multi-step processing to yield mature lamin A. It is of utmost importance to characterize the prelamin A form accumulated in each laminopathy, since existing evidence shows that drugs acting on protein processing can improve some pathological aspects. We report that two antibodies raised against differently modified prelamin A peptides show a clear specificity to full-length prelamin A or carboxymethylated farnesylated prelamin A, respectively. Using these antibodies, we demonstrated that inhibition of the prelamin A endoprotease ZMPSTE24 mostly elicits accumulation of full-length prelamin A in its farnesylated form, while loss of the prelamin A cleavage site causes accumulation of carboxymethylated prelamin A in progeria cells. These results suggest a major role of ZMPSTE24 in the first prelamin A cleavage step.

Citing Articles

Effect of β-Estradiol on Adipogenesis in a 3T3-L1 Cell Model of Prelamin A Accumulation.

Cobelo-Gomez S, Sanchez-Iglesias S, Fernandez-Pombo A, Araujo-Vilar D Int J Mol Sci. 2024; 25(2).

PMID: 38279282 PMC: 10816192. DOI: 10.3390/ijms25021282.

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