| NUP153 is a nuclear basket–associated nucleoporin that forms part of the nuclear pore complex (NPC), a multi‑protein channel embedded in the nuclear envelope that mediates selective nucleocytoplasmic transport of proteins, mRNAs, and ribonucleoprotein complexes. NUP153 contains an N‑terminal channel‑interacting domain, a central region that mediates interactions with other nucleoporins, and a C‑terminal FG‑repeat and DNA‑binding‑like module that projects from the nuclear face of the NPC and can contact chromatin and transcription‑regulatory complexes. NUP153 functions as a scaffold for the nuclear basket, helping to organize transport receptors and soluble factors near the NPC and contributing to mRNA quality control by retaining unspliced or improperly processed transcripts within the nucleus. NUP153 binds near transcriptional start sites of developmental and lineage‑specific genes at genomic regions distinct from canonical polycomb‑marked sites, and this binding is required for the recruitment of polycomb repressive complex 1 (PRC1) to a subset of these loci, where PRC1 deposits H2AK119ub1 and maintains transcriptional repression. Depletion of NUP153 in these cells causes derepression of early differentiation‑related genes, precocious activation of neuroectodermal and other lineage programs, and loss of pluripotency without overt disruption of nuclear import of core pluripotency transcription factors, indicating that NUP153 acts as a site‑specific chromatin‑associated regulator rather than solely as a passive transport element. |
Lane 1: K562, Lane 2: MCF7, Lane 3: A549, Lane 4: COS-7
