Researches Identify New Therapeutic Targets for Carcinogenic Drugs

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Researchers from Oregon State University (OSU) identify new targets in molecular motors that are expected to pave the way toward new cancer therapies.

A kinesin is a motor protein found in eukaryotic cells interacting with microtubules inside cells. The active movement of kinesins convert chemical energy into mechanical energy, which in turn generates the directional movements and forces necessary to sustain life. Kinesins provide anterograde transport- a process in which kinesins tend to walk towards the positive end of a microtubule to transport cargos of proteins and various membrane components from the center of the cell towards the periphery. Kinesin-14s subgroup preferentially binds to two different microtubules. It is achieved by binding one microtubule the protein’s feet, and the other microtubule with its tail. Such behavior of preference in kinesins was not identified earlier. However, researchers in the OSU College of Science suggested that some kinesin-14s are characterized by a stiff waist, which enables these motor proteins to prefer a two-microtubule track. The research published in the journal Current Biology on July 12, 2018, is significantly important as certain cancer cells depend on kinesin-14 to proliferate and grow in a host. New therapeutic drugs capable of making the kinesins elastic, can grinding the molecular motor to a halt and eventually eliminate the cancer cells.

The researchers observed that Kinesin-14s are responsible for the assembly spindles, which are cytoskeletal structures of eukaryotic cells formed during cell division. These spindles function to separate sister chromatids between daughter cells. The kinesin-14s were isolated from a fungus and a fruit fly. The waist part was cut open to insert a flexible polypeptide linker. It was found that fungal kinesin-14 motor moved toward the minus end of the microtubules, instead of the plus end. Furthermore, the fly’s kinesin-14 motor was progressive, minus-end-directed motor. However, fruit fly kinesin-14 did not bind to two microtubules due to a flexible waist. The researchers stated that new therapeutic approach that is capable of targeting the waist region of the motor protein could eliminate cancer cells.

 

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