Disease relevance of KIF2C

• In contrast, 9 of 9 colon cancer specimens showed overexpression of KNSL6 mRNA, ranging from 5 to 44 times the level detected in normal colon tissue, indicating that this antigen could also be a valuable therapeutic target [1].
• These findings suggest the involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer [2].

High impact information on KIF2C

• We propose that the chromosomal passenger complex regulates local MCAK activity to permit spindle formation via stabilization of chromatin-associated microtubules [3].
• The Kin I kinesins are microtubule-destabilizing enzymes important for neuronal transport, spindle assembly, and chromosome segregation. now show that the Kin I MCAK is a microtubule end-stimulated ATPase that can catalytically depolymerize MT's [4].
• MCAK has one high-affinity binding site per protofilament end, which, when occupied, has both the depolymerase and ATPase activities [5].
• Tip tracking of MCAK is inhibited by phosphorylation and is dependent on the extreme COOH-terminal tail of MCAK [6].
• Bipolar spindle assembly was restored in cells lacking Kif2a by treatments that altered microtubule assembly (nocodazole), eliminated kinetochore-microtubule attachment (loss of Nuf2), or stabilized microtubule plus ends at kinetochores (loss of MCAK) [7].

Biological context of KIF2C

• Thus, two KinI motors, MCAK and Kif2a, play distinct roles in mitosis, and MCAK activity at kinetochores must be balanced by Kif2a activity at poles for spindle bipolarity [7].
• At prophase MCAK is recruited to mitotic centromeres [8].
• Mitotic centromere-associated kinesin (MCAK) is important for anaphase chromosome segregation [8].
• MCAK is diffusely localized to both the cytoplasm and the nucleus during interphase [8].
• The HsMCAK gene has a predicted 723 amino acid open reading frame, encoding a 81 kDa protein that shares 79.2% homology with hamster MCAK [9].

Anatomical context of KIF2C

• MCAK associates with the tips of polymerizing microtubules [6].
• MCAK, a Kin I kinesin, increases the catastrophe frequency of steady-state HeLa cell microtubules in an ATP-dependent manner in vitro [10].
• MCAK protein is present in interphase and mitotic CHO cells and is transcribed as a single 3.4-kb message [11].
• The first involves a role for TOGp in protecting spindle MTs from MCAK activity at the centrosome, which appears essential to prevent the formation of disorganized multipolar spindles [12].
• With regard to KNSL6 mRNA expression, only trace levels were detected in 15 different normal tissues with the exception of testis, which showed a high level of KNSL6 mRNA expression [1].

Associations of KIF2C with chemical compounds

• We found that deletions and alanine substitutions of highly conserved positively charged residues in the MCAK neck domain significantly reduced MT depolymerization activity [13].
• The Interplay of the N- and C-Terminal Domains of MCAK Control Microtubule Depolymerization Activity and Spindle Assembly [14].

Other interactions of KIF2C

• MCAK is a homodimer that is encoded by a single gene and has no associated subunits [15].

Analytical, diagnostic and therapeutic context of KIF2C

• Sequence analysis shows MCAK to be a kinesin-related protein with the motor domain located in the center of the protein [11].
• Molecular dissection of the microtubule depolymerizing activity of mitotic centromere-associated kinesin [16].
• We have characterized the immunofluorescence localization of centromere-bound MCAK and found that MCAK localized to inner kinetochores during prophase but was predominantly centromeric by metaphase [17].

References