Disease relevance of KIF4A

• Studies performed with mammalian cell systems confirmed that the HIV-1 Gag protein associates with KIF-4 [1].
• These results, and our previous studies, raise the possibility that KIF-4 may play an important role in retrovirus Gag protein transport [1].
• These observations imply a deregulation of chromokinesin in retinoblastoma cells [2].

High impact information on KIF4A

• When neurons are stimulated by membrane depolarization, calcium signaling mediated by CaMKII induces dissociation of KIF4 from PARP-1, resulting in upregulation of PARP-1 activity, which supports neuron survival [3].
• Here, we report that the activity-dependent prevention of apoptosis in juvenile neurons is regulated by kinesin superfamily protein 4 (KIF4), a microtubule-based molecular motor [3].
• After dissociation from PARP-1, KIF4 enters into the cytoplasm from the nucleus and moves to the distal part of neurites in a microtubule-dependent manner [3].
• The C-terminal domain of KIF4 is a module that suppresses the activity of poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme known to maintain cell homeostasis by repairing DNA and serving as a transcriptional regulator [3].
• Inactivation of the chromokinesin hKid, by RNAi or antibody microinjection, prevented the formation of stable bipolar spindles and the 'metaphase-like' alignment of chromosomes in cells expressing stable cyclinB1 [4].

Biological context of KIF4A

• Our results provide functional evidence that human KIF4A is a novel component of the chromosome condensation and segregation machinery functioning in multiple steps of mitotic division [5].
• Assignment of the kinesin family member 4 genes (KIF4A and KIF4B) to human chromosome bands Xq13.1 and 5q33.1 by in situ hybridization [6].
• A large portion of human kinesin superfamily protein member 4 (KIF4) is associated with the nuclear matrix during the interphase, while a small portion is found in the cytoplasm [7].
• During mitotic phase of cell cycle, KIF4 appears to colocalize with membranous organelles in the mitotic spindle [8].
• Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis [9].

Anatomical context of KIF4A

• KIF4 protein has the property of nucleotide-dependent binding to microtubules, microtubule-activated ATPase activity, and microtubule plus-end-directed motility [8].
• A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally [8].
• Immunocytochemical studies revealed that KIF4 colocalized with membranous organelles both in growth cones of differentiated neurons and in the cytoplasm of cultured fibroblasts [8].
• As an initial step to understand the function(s) of human KIF4, its subcellular localization in HeLa cells was examined by using immunocytochemical and subcellular fractionation methods, and it was found that most KIF4 is localized in the nucleus [10].
• Since murine KIF4 is known to transport cytoplasmic vesicles, dominant nuclear localization of the human counterpart was somewhat surprising [10].

Physical interactions of KIF4A

• Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation [11].

Co-localisations of KIF4A

• Further more, DNMT3B co-localizes with condensin and KIF4A on condensed chromosomes throughout mitosis [12].

Other interactions of KIF4A

• The co-fractionation experiment revealed that KIF4 and BRAF35 were present in a complex of approx. 540 kDa [7].
• Of these, only KIF14, a putative chromokinesin, was overexpressed in various cancers by real-time RT-PCR [13].
• To directly test this hypothesis, two putative downstream targets of the Ran spindle assembly pathway, TPX2, a protein required for correct spindle assembly and Kid, a chromokinesin involved in chromosome arm orientation on the spindle, were analyzed to determine if their direct binding to nuclear transport receptors inhibited their function [14].
• Chromokinesin Kid (kinesin-like DNA-binding protein) localizes on spindles and chromosomes and has important roles in generating polar ejection force on microtubules in the metaphase [15].

Analytical, diagnostic and therapeutic context of KIF4A

• In the present study, we identified a protein that interacts with KIF4 using a yeast two-hybrid system, co-immunoprecipitation and co-fractionation [7].
• Northern blot analysis and in situ hybridization demonstrated that KIF4 is strongly expressed in juvenile tissues including differentiated young neurons, while its expression is decreased considerably in adult mice except in spleen [8].
• Using the yeast two-hybrid assay, we also found an association of KIF-4 with Gag proteins of Mason-Pfizer monkey virus (MPMV), simian immunodeficiency virus (SIV), and human immunodeficiency virus type 1 (HIV-1) [1].

References