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Mutations in the CASC5 gene were found to encode a kinetochore protein essential for mitotic cell division and to cause autosomal recessive primary microcephaly 4. (Review)
Therefore, Mps1 (显示 IDUA 蛋白) promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1 (显示 BUB1 蛋白), and Mad1 (显示 MXD1 蛋白). This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 (显示 IDUA 蛋白) and to kinetochore-microtubule attachment.
CASC5 may contribute to the morphological and structural changes of the human brain during recent evolution. The observed between-population divergence of CASC5 variants was driven by natural selection that tends to favor a larger gray matter volume in East Asians.
Involvement of CASC5 in autosomal recessive microcephaly and a founder effect of the c.6125G>A mutation.
Targeted Knockdown of the Kinetochore Protein D40/Knl-1 Inhibits Human Cancer in a p53 (显示 TP53 蛋白) Status-Independent Manner
We propose that CASC5 has a key role for the correct functioning of DNA damage response proteins, and a defect in this connection might affect upstream and downstream DNA damage response events as response to increased genotoxic stress.
Data show sequential multisite regulation of the microtubule-associated protein KNL1-kinase-adaptor complex BUB1 (显示 BUB1 蛋白)/BUB3 (显示 BUB3 蛋白) interaction.
Mechanisms of mitosis-specific assembly of the checkpoint platform Knl1/MIS12 (显示 MIS12 蛋白)/NDC80 (显示 NDC80 蛋白) at human kinetochores.
PP2A (显示 PPP2R4 蛋白)-B56 is a key phosphatase for the removal of the Mps1 (显示 IDUA 蛋白)-mediated Knl1 phosphorylations necessary for Bub1/BubR1 (显示 BUB1B 蛋白) recruitment in mammalian cells.
Protein phosphatase 1 (PP1) binding to KNL1 during prometaphase reduces the levels of Bub proteins at kinetochores to approximately the level recruited by four active MELT repeats.
Data indicate that microtubule-associated proteins KNL-1 oligomerization may coordinate with other kinetochore activities to ensure the proper organization, function, and sensory capabilities of the kinetochore-microtubule attachment.
KNL-1 plays a central role in translating the initiation of kinetochore assembly
The protein encoded by this gene is a component of the multiprotein assembly that is required for creation of kinetochore-microtubule attachments and chromosome segregation. The encoded protein functions as a scaffold for proteins that influence the spindle assembly checkpoint during the eukaryotic cell cycle and it interacts with at least five different kinetochore proteins and two checkpoint kinases. In adults, this gene is predominantly expressed in normal testes, various cancer cell lines and primary tumors from other tissues and is ubiquitously expressed in fetal tissues. This gene was originally identified as a fusion partner with the mixed-lineage leukemia (MLL) gene in t(11\;15)(q23\;q14). Mutations in this gene cause autosomal recessive primary microcephaly-4 (MCPH4). Alternative splicing results in multiple transcript variants encoding different isoforms. Additional splice variants have been described but their biological validity has not been confirmed.
cancer susceptibility candidate 5
, ALL1-fused gene from chromosome 15q14 protein
, blinkin, bub-linking kinetochore protein
, cancer susceptibility candidate gene 5 protein
, cancer/testis antigen 29
, kinetochore null 1 homolog
, kinetochore-null protein 1
, protein CASC5
, protein phosphatase 1, regulatory subunit 55
, RAD51 homolog