Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) (NUCKS1)

Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) is a highly phosphorylated, chromatin-associated protein that plays a vital role in maintaining genomic stability and regulating the eukaryotic cell cycle. It is primarily localized in the nucleus, where it functions as a DNA-binding protein and a transcriptional regulator, notably influencing the insulin signaling pathway and critical oncogenic axes such as PI3K/AKT/mTOR [1, 3, 6]. In oncology, NUCKS1 is frequently overexpressed and acts as an oncogene, promoting proliferation, invasion, and metastasis across multiple malignancies including lung, hepatocellular, and colorectal cancers [5, 8, 9]. Its involvement in DNA double-strand break repair via the homologous recombination pathway, specifically by interacting with RAD51 and RAD54, suggests that its inhibition could sensitize tumor cells to DNA-damaging agents [1, 10]. While direct small-molecule inhibitors for clinical use are currently lacking, experimental therapeutic strategies focus on mRNA knockdown using antisense oligonucleotides or RNA interference to mitigate its pro-tumorigenic effects [4, 6, 16]. However, its ubiquitous expression throughout normal tissues presents a significant challenge for therapeutic development, necessitating targeted delivery systems to avoid broad systemic toxicity [1, 3].

Other names

JC7P1NUCKSPotential LAG1 interactor

Experimental strategies target the NUCKS1 mRNA for degradation or translation inhibition using RNA interference (siRNA/shRNA) or antisense oligonucleotides to reduce the expression of the NUCKS1 protein, thereby inhibiting oncogenic signaling pathways such as PI3K/AKT/mTOR and impairing DNA repair capacity in malignant cells.