Progerin-lamin A interaction

Progerin-lamin A interaction" refers to the aberrant, pathological binding between **progerin**, a mutant truncated form of **lamin A** (produced by LMNA gene mutation), and wild-type lamin A. Progerin results from activation of a cryptic splice site in LMNA, causing loss of the ZMPSTE24 cleavage site and persistent farnesylation. This interaction is central in the pathogenesis of Hutchinson-Gilford progeria syndrome (HGPS), where progerin binds lamin A/C with increased affinity relative to normal lamin A–lamin A interaction, disrupting the nuclear lamina, inducing irregular nuclear shape, genomic instability, abnormal chromatin organization, decreased proliferative capacity, abnormal DNA replication, defective nucleoplasmic protein composition, and premature cellular senescence[1][2][3][5]. Progerin does not interact normally with all lamin A partners (e.g., has weakened binding for LAP2α)[3], and also traps factors like PCNA, contributing to genomic instability[1]. Disruption of progerin–lamin A interaction by small molecules (such as progerinin/JH4 or FTIs) can restore certain nuclear and cellular defects in HGPS models, making this interaction a research therapeutic target, but not itself a molecule, enzyme, or receptor[6][5]. Notes: - "Progerin-lamin A interaction" is **not** a single molecule, protein, enzyme, or canonical therapeutic target, but an aberrant protein–protein interaction central to HGPS pathology. - Proper canonical targets would be "progerin" (mutant lamin A) or "lamin A" (wild-type), both intermediate filament proteins of the nuclear envelope. - Because of this, the entity described is not suitable for structured target databases that expect a single molecule (e.g., a receptor or enzyme).

Other names

Lamin A–progerin interactionprogerin–lamin A binding

Inhibition of aberrant interaction (small molecules preventing progerin–lamin A binding), Inhibition of progerin farnesylation