The Sequence [RRKLPVGRS] Is a Nuclear Localization Signal for Importin 8 Binding (NLS8): A Chemical Biology and Bioinformatics Study.

Christos A Panagiotidis, Dimitris Dellis, Elias Castanas, Konstantina Kalyvianaki, Athanasios A Panagiotopoulos, Marilena Kampa, Aikaterini Angelidaki

Journal: International journal of molecular sciences 2025;26(6):

PMID: 40141456

Abstract

Karyopherins, carrier proteins that recognize particular cargo protein patterns known as nuclear localization signals (NLSs), mediate the nuclear translocation of big proteins. In order to better understand the process of nuclear transport of proteins and create the groundwork for the development of innovative treatments that specifically target importins, it is imperative to clarify the intricate interactions between nuclear transporters and their cargo proteins. Until recently, very few NLSs have been documented. In the current work, an in silico method was used to identify NLSs for importin 8. It was determined that the sequence RRKLPVGRS serves as a recognition motif for importin 8 binding a karyopherin that is involved in the nuclear transportation of several important proteins like AGOs, SMADs, RPL23A, and TFE3. The sequence was validated in vitro in the breast cancer cell line T47D. This work subscribes to the effort to clarify the intricate relationships between nuclear transporters and their cargo proteins, in order to better understand the mechanism of nuclear transport of proteins and lay the groundwork for the development of novel therapeutics that target particular importins and have an immediate translational impact.

Address: Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, Voutes Campus, 71013 Heraklion, Greece.; National Infrastructures for Research and Technology, 11523 Athens, Greece.; Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
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