Disease relevance of Kif5b

• Altered expression of ubiquitous kinesin heavy chain results in resistance to etoposide and hypersensitivity to colchicine: mapping of the domain associated with drug response [1].
• We analyzed the effects of retroviral transduction of the human uKHC and its derivatives on drug sensitivity of the human fibrosarcoma cell line HT1080 [1].
• Successful simultaneous transplants of a cancer of the ascending colon from a 60 year old woman, taken from 3 sites: the primary focus, a lymph node metastasis, and a hepatic metastasis, into nude mice yielded KHC (-P, -N, -H) strains [2].

Psychiatry related information on Kif5b

• While KHC contains the motor activity, the role of KLC remains unknown [3].

High impact information on Kif5b

• To analyze the significance of this conventional kinesin heavy chain in organelle transport, we studied the distribution of major organelles in the extraembryonic cells [4].
• Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria [4].
• To test the hypothesis that fast anterograde molecular motor proteins power the slow axonal transport of neurofilaments (NFs), we used homologous recombination to generate mice lacking the neuronal-specific conventional kinesin heavy chain, KIF5A [5].
• Defective kinesin heavy chain behavior in mouse kinesin light chain mutants [3].
• Expression of the human kinesin heavy-chain gene was decreased in four of four etoposide-resistant HeLa cell lines, derived by conventional drug selection, indicating that downregulation of kinesin represents a natural mechanism of drug resistance in mammalian cells [6].

Biological context of Kif5b

• Surprisingly, overexpression of full-length uKHC and its variants that were deficient in the NH2-terminal motor domain produced a phenotype similar to that of antisense RNA, characterized by resistance to etoposide and collateral sensitivity to colchicine [1].
• Expression of all the members of the KLC (A-C) family and dynein was up-regulated during nerve regeneration, whereas the abundant expression of the neuron-specific KHC mRNA was not changed [7].

Anatomical context of Kif5b

• KLC3 can be classified as a genuine light chain: it interacts in vitro with the KHC, the interaction is mediated by a conserved heptad repeat sequence, and it associates in vitro with microtubules [8].
• Suppression of the expression of a pancreatic beta-cell form of the kinesin heavy chain by antisense oligonucleotides inhibits insulin secretion from primary cultures of mouse beta-cells [9].
• The latter technique allowed us to demonstrate a close association between kinesin heavy chain, microtubuli, and melanosomes [10].
• In fat-fed C57BL/6 mice, chow fed apo E-/- mice and KHC rabbits, the various ACAT inhibitors had either no effect or increased indices of atherosclerotic foam cell formation [11].

Physical interactions of Kif5b

• Both the kinesin light chain kinase and phosphatase co-purify with the kinesin heavy chain, suggesting that kinesin exists in a large complex capable of self-regulation [12].

Other interactions of Kif5b

• By a proteomic approach, we demonstrated in rat coagulating gland secretion the presence of a 120 kDa protein which shares at least 80% identity at the amino acid level with the most closely related kinesin heavy chain codified by the kinesin superfamily protein Kif5c gene [13].

Analytical, diagnostic and therapeutic context of Kif5b

• Co-immunoprecipitation with a monoclonal kinesin heavy chain antibody precipitated both alpha- and beta-dystrobrevin, indicating that this interaction is not restricted to the beta-dystrobrevin isoform [14].
• Western immunoblotting confirmed the close antigenic homology between CK and SUK, using a mouse monoclonal sea urchin kinesin heavy chain-specific antibody (SUK 4) [15].

References