TI - The role of a nuclear derived spindle matrix in mitotic control . AB - Overall , our results support a model in which Mtor/Tpr acts as a spatial regulator of SAC , ensuring a timely and effective recruitment of Mad2 and Mps1 to unattached KTs as cells enter mitosis ( Fig 5 J ) . In budding yeast , Mps1 PHOSphorylates Mad1 , which is continuously recycled to KTs from Mlps at NPCs , but N-terminal deletion mutants of Mad1 lacking the Mlp -binding domain have a functional SAC . In humans and Drosophila , Mps1 regulates Mad2 at KTs . Because Mad1 localization at KTs does not depend on Mlps/Mtor/Tpr and Mps1 kinase activity , the residual Mad2 at KTs after Mtor/Tpr RNAi possibly corresponds to the Mad1-bound fraction . One possibility is that Mps1 PHOSphorylation of Mad1 regulates the recruitment of a fast-exchanging pool of Mad2 to KTs ( Chung and Chen , 2002 ; Musacchio and Salmon , 2007 ) . Parallelly , Mtor/Tpr may spatially regulate Mps1 autoPHOSphorylation , which is important for its normal KT accumulation , together with Mad2 . The presence of Mad2 in the complex may work as a positive feedback mechanism to ensure continuous Mps1 kinase activity upon SAC activation . SAC proteins evolved from systems with a closed mitosis like budding yeast , where the spindle assembles inside an intact nuclear envelope into more complex systems like animals and plants , where the nuclear envelope is thought to fully or partially disintegrate during spindle formation , justifying the requirement of a nuclear derived spindle matrix for an effective SAC response . What retains matrix components around the spindle in systems where mitosis is thought to be open remains an intriguing question . In this regard , lamin B was proposed to tether several factors that mediate spindle assembly in Xenopuslaevis egg extracts and possibly in human cells . Additionally , a continuous endoplasmic reticulum surrounding the mitotic spindle is thought to be recycled from the nuclear envelope after its disassembly and has been observed in many systems undergoing an open mitosis , including humans . Although such fenestrated membranous systems cannot work as diffusion barriers , it is possible that they indirectly help to generate local gradients or concentrate matrix-affine SUBstrates ( Fig 5 J ) . The enrichment of Mad2 in the spindle matrix provides an explanation for an unsolved SAC paradigm in which the "wait anaphase" signal emanating from unattached KTs must be diffusible to prevent premature anaphase onset of already bioriented chromosomes but at the same time is known to be restricted to the vicinity of the spindle . The proposed role of Mtor/Tpr further supports the necessity of spindle maturation for proper KT-MT attachments and anaphase spindle elongation in which the spindle matrix may help extend the duration of mitosis for the assembly of a competent chromosome segregation machinery . Mtor/Tpr-depleted cells have a weakened SAC response that , as opposed to complete checkpoint loss , may be compatible with cell viability and lead to cancer . The involvement of Tpr in the activation of several oncogenes may translate into an unfavorable combination that facilitates transformation and tumorigenesis in humans .