Disease relevance of KIF20A

• Down-regulation of RAB6KIFL/KIF20A, a kinesin involved with membrane trafficking of discs large homologue 5, can attenuate growth of pancreatic cancer cell [1].
• RAB6KIFL maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no mutations of RAB6KIFL in malignant myeloid disorders with loss of 5q [2].

High impact information on KIF20A

• The Rab6-binding kinesin, Rab6-KIFL, is required for cytokinesis [3].
• Microinjection of antibodies to Rab6-KIFL results in the cells becoming binucleate after one cell cycle, and time-lapse microscopy reveals that this is due to a defect in cleavage furrow formation and thus cytokinesis [3].
• Overexpression of Rab6-KIFL causes a cell division defect resulting in cell death [3].
• We find that Rab6-KIFL accumulates in mitotic cells where it localizes to the midzone of the spindle during anaphase, and to the cleavage furrow and midbody during telophase [3].
• Here we describe a new mitotic human kinesin-like protein, RB6K (Rabkinesin 6), distantly related to MKLP-1 [4].

Biological context of KIF20A

• The RAB6KIFL gene is mapped to human chromosome 5, band q31, spans approximately 8.5kb of genomic DNA, and contains 19 exons [2].

Anatomical context of KIF20A

• Knockdown of endogenous RAB6KIFL expression in PDAC cell lines by small interfering RNA drastically attenuated growth of those cells, suggesting an essential role for the gene product in maintaining viability of PDAC cells [1].
• RAB6KIFL belongs to the kinesin superfamily of motor proteins, which have critical functions in trafficking of molecules and organelles [1].
• Decreased levels of endogenous RAB6KIFL in PDAC cells altered the subcellular localization of DLG5 from cytoplasmic membranes to cytoplasm [1].
• Since the GTP-bound form of Rab6B (Rab6B Q72L) does interact with all known Rab6A effectors, including Rabkinesin-6, the results suggest a cell-type specific role for Rab6B in retrograde membrane traffic at the level of the Golgi complex [5].
• Here we outline biochemical assays for studying the interaction of Rabkinesin-6/Rab6-KIFL/MKlp2 with microtubules, and its regulation and interaction with the mitotic polo-like kinase 1 using recombinant proteins expressed in and purified from insect cells [6].

References