Heat shock protein nuclear import factor hikeshi mRNA (HIKESHI mRNA)

HIKESHI (Heat shock protein nuclear import factor hikeshi) is a specialized nuclear transport receptor that mediates the translocation of 70 kDa heat-shock proteins (Hsp70s) from the cytoplasm to the nucleus, particularly under heat stress conditions. It functions as an asymmetric homodimer that interacts with FG-nucleoporins of the nuclear pore complex to facilitate the entry of ATP-bound Hsp70, which is essential for protecting nuclear proteostasis and regulating the heat shock response. Mutations in the HIKESHI gene are the underlying cause of Hypomyelinating Leukodystrophy 13 (HLD13), a severe neurodegenerative disorder characterized by impaired myelination and extreme sensitivity to febrile illness. In the context of oncology, HIKESHI is frequently overexpressed in various malignancies, such as gastric, renal, and prostate cancers, where it contributes to thermotolerance and tumor progression. Consequently, HIKESHI mRNA is being investigated as a therapeutic target using small interfering RNAs (siRNAs) to silence its expression and sensitize cancer cells to hyperthermia-based treatments. This strategy aims to abrogate the protective nuclear function of Hsp70, thereby enhancing the cytotoxic effects of thermal stress in refractory tumors.

Other names

C11orf73 mRNAChromosome 11 open reading frame 73 mRNAHSPC138 mRNAHSPC179 mRNAL7RN6 mRNAOPI10 mRNAHLD13 mRNA

RNA interference (RNAi) mediated degradation of HIKESHI mRNA, leading to reduced protein levels and subsequent inhibition of HSP70 nuclear import.