Disease relevance of ZW10

• These results are consistent with the hypothesis that the abnormal expression of genes involved in maintaining the mitotic spindle checkpoint and genomic stability, e.g., hBUB3, hZW10, and APC2, contribute to the molecular pathogenesis and tumor progression of tobacco smoke-induced adenocarcinoma of the lung [1].

High impact information on ZW10

• Zeste white 10 (ZW10) is a mitotic checkpoint protein and the anchor for cytoplasmic dynein at mitotic kinetochores, though it is expressed throughout the cell cycle [2].
• Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function [2].
• ZW10 RNAi also dispersed endosomes and lysosomes [2].
• Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) caused Golgi dispersal [2].
• We find that ZW10 localizes to pericentriolar membranous structures during interphase and cosediments with Golgi membranes [2].

Associations of ZW10 with chemical compounds

• We therefore conclude that Aurora B kinase activity is required for the accumulation of tension-sensitive mitotic-checkpoint components, such as hZW10 and hROD, in order to maintain mitotic-checkpoint arrest [3].

Biological context of ZW10

• ZW10, a dynamitin-interacting protein associated with kinetochores, is known to participate directly in turning off of the spindle checkpoint [4].
• The present results disclose an unexpected role for a spindle checkpoint protein, ZW10, during interphase [4].
• As ZW10 and Zwint-1 are absent from yeast, we reasoned that metazoans evolved an elaborate spindle checkpoint machinery to ensure faithful chromosome segregation in mitosis [5].
• However, the excess CENP-C does not disrupt the native centromeres detectably and does not associate with another conserved centromere protein, ZW10 [6].
• Thus, ZW10 functions as a linker between the core structural elements of the outer kinetochore and components that catalyze generation of the mitotic checkpoint-derived "stop anaphase" inhibitor [7].

Anatomical context of ZW10

• Implication of ZW10 in membrane trafficking between the endoplasmic reticulum and Golgi [4].
• Here we show that Zwint-1 is required and is sufficient for kinetochore localization of Zeste White 10 (ZW10) in HeLa cells [5].
• We also find ZW10 enriched at the leading edge of migrating fibroblasts, suggesting that ZW10 serves as a general regulator of dynein function throughout the cell cycle [2].
• Zwilch localizes to kinetochores and kinetochore microtubules in a manner identical to ZW10 and ROD [8].

Physical interactions of ZW10

• In contrast, no redistribution or release of RINT-1 from the syntaxin 18 complex was observed when ZW10 expression was reduced [9].
• HZwint-1 (Human ZW10 interacting protein-1) was identified in a yeast two hybrid screen for proteins that interact with HZW10 [10].
• The human Zwilch protein (hZwilch) coimmunoprecipitates with hZW10 and hROD from HeLa cell extracts and localizes to the kinetochores at prometaphase [8].

Regulatory relationships of ZW10

• RINT-1 regulates the localization and entry of ZW10 to the syntaxin 18 complex [9].
• Dominant-negative expression of guanosine diphosphate-Rab6 suppressed ZW10 knockdown induced-Golgi disruption [11].

Other interactions of ZW10

• Zwint-1 specifies the kinetochore association of ZW10 by interacting with its N-terminal domain [5].
• ZW10 and Rod play an essential role in this checkpoint [7].
• The sequence-specific DNA-binding protein CENP-B and the microtubule-associated proteins CENP-E and HZW10 were not recruited, and neocentromeric activity was not detected [12].
• In addition, INCENP, ZWINT-1, ZW10 antisense-treated chromosome morphology was very similar to that of Roberts chromosome when analysed by atomic force microscopy [13].

Analytical, diagnostic and therapeutic context of ZW10

• Overexpression, microinjection and knockdown experiments revealed that ZW10 is involved in membrane trafficking between the endoplasmic reticulum and Golgi [4].
• This study presents the results of tests that were carried out at the Institutes for Desert Research, Kiryat Sde-Boker, Israel, and focused on the influence of hydrodynamic conditions on fouling in a pilot-scale immersed membrane bioreactor (IMBR) using a hollow fiber membrane module of ZW-10 (Zenon Environmental, Canada) under ambient conditions [14].

References