The STARD9/Kif16a Kinesin Associates with Mitotic Microtubules and Regulates Spindle Pole Assembly
Open accessAbstract
During cell division, cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule copurifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential antimitotic target.
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STARD9 had moderate growth defects when knocked out in all cell lines except those with a KRAS G12D mutation.
“STARD9, a gene encoding a kinesin required for mitotic spindle assembly69, had moderate growth defects when knocked out in all cell lines except those with a KRAS G12D mutation”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [69]
Other genes with protein-coding SNCs (NEK6, STARD9/KIF16A and CDK5RAP2) are implicated in the regulation of spindle pole assembly.
“Other genes with protein-coding SNCs (NEK6, STARD9/KIF16A and CDK5RAP2) turn out to be implicated in the regulation of spindle pole assembly as well62–64.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [63]
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References 53 · Cited by 80
- Authors
- Torres, J. Z., Summers, M. K., Peterson, D., Brauer, M. J., Lee, J., Senese, S., Gholkar, A. A., Lo, Y.-C., Lei, X., Jung, K., Anderson, D. C., Davis, D. P., Belmont, L., & Jackson, P. K.
- Affiliations
- University of California, Los Angeles (US)
- Genentech (US)
- University of Oregon (US)
- Corresponding author
- Torres, Jorge Z.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 147
- Issue
- 6
- Pages
- 1309-1323
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4180425
- OpenAlex
- W2031805768
- Cited by
- 80
- References
- 53
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 9 · 2020: 5 · 2019: 8 · 2018: 1 · 2017: 7 · 2016: 9 · 2015: 8 · 2014: 11 · 2013: 3 · 2012: 4
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 630 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM054811, R01GM063023)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- kinesin-3, mitotic spindle assembly, pericentriolar material, centrosome, spindle assembly checkpoint, multipolar spindles, mitotic arrest, apoptosis, paclitaxel
- MeSH terms
- Amino Acid Sequence, Carrier Proteins, Centrioles, HeLa Cells, Humans, Microtubule Proteins, Microtubules, Mitosis, Spindle Apparatus, Molecular Sequence Data, Neoplasms, Phylogeny, Sequence Alignment, Apoptosis, Proteome, Cell Line, Tumor
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