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Showing DNAI7 — LAS1 is a alias.

DNAI7

Dynein axonemal intermediate chain 7 · UniProt Q6TDU7

Length
716 aa
Mass
83.2 kDa
Annotated
2026-06-09
22 papers in source corpus 4 papers cited in narrative 3 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 3/3 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAI7 (CASC1/CFAP94/PPP1R54) is an intermediate chain of the flagellar inner dynein arm IDA f/I1 complex and, in mammalian cells, a regulator of mitotic microtubule dynamics with tumor-suppressive activity. In Chlamydomonas, its ortholog IC97 is required for normal flagellar beat frequency and for coordination between the two flagella, and its loss produces slow swimming and beat miscoordination without abolishing phototaxis, defining a role in ciliary/flagellar motility (PMID:39601552). In mammalian cells, CASC1 is required for microtubule polymerization and satisfaction of the spindle assembly checkpoint, and its depletion sensitizes paclitaxel-resistant lung cancer cells to spindle poisons and inhibits tumor growth in vivo (PMID:24860162). Casc1 also acts as a tumor suppressor in vivo, where its loss increases susceptibility to chemically induced lung tumors and an allelic variant modulates cancer cell growth (PMID:16862160, PMID:16458428). Beyond these motility and mitotic roles, no further mechanistic detail has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2006 Medium

    Established that CASC1 functions as a lung tumor suppressor in vivo, defining its physiological relevance to cancer susceptibility.

    Evidence Casc1 knockout mouse chemical-induction tumor bioassay plus allele-specific in vitro colony formation in human lung cancer cell lines

    PMID:16458428 PMID:16862160

    Open questions at the time
    • Molecular mechanism linking CASC1 loss to tumorigenesis not defined
    • Allele-specific growth effect not mechanistically explained beyond exclusion of apoptosis
  2. 2014 Medium

    Connected CASC1 to mitotic spindle function, showing it is required for microtubule polymerization and spindle assembly checkpoint satisfaction and that its loss can resensitize drug-resistant tumor cells.

    Evidence Genome-wide RNAi screen with live-cell imaging of mitotic fate and in vivo xenograft growth assay in NSCLC cells

    PMID:24860162

    Open questions at the time
    • Direct biochemical interaction of CASC1 with microtubules or checkpoint proteins not demonstrated
    • Single-lab RNAi without genetic rescue
    • Relationship between this mitotic role and the dynein/flagellar role unresolved
  3. 2024 Medium

    Identified the molecular identity of the DNAI7 ortholog as an IDA f/I1 inner dynein arm intermediate chain governing flagellar beat frequency and inter-flagellar coordination.

    Evidence Chlamydomonas ic97 null mutant with flagellar motility, beat frequency, and coordination phenotyping plus biochemical analysis of IDA f/I1 assembly

    PMID:39601552

    Open questions at the time
    • Direct evidence for an analogous dynein role in human cells absent
    • How the same protein reconciles flagellar dynein and mitotic spindle functions unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether the mammalian mitotic/tumor-suppressor role and the conserved flagellar dynein intermediate-chain role reflect a single unified molecular activity remains unresolved.
  • No structural model of human DNAI7 in either context
  • Direct binding partners in human cells not identified
  • Tissue-specific functions of motility vs mitotic roles not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 1 GO:0005929 cilium 1
Pathway
R-HSA-1640170 Cell Cycle 1
Complex memberships
inner dynein arm IDA f/I1

Evidence

Reading pass · 3 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 CASC1 (PPP1R54/DNAI7 alias) is essential for microtubule polymerization and satisfaction of the spindle assembly checkpoint in NSCLC cells; RNAi-mediated attenuation of CASC1 sensitized paclitaxel-resistant cells to spindle poisons and inhibited tumor growth in vivo. Genome-wide RNAi screen combined with live-cell imaging to measure mitotic fate; in vivo xenograft growth assay after RNAi knockdown Cancer research Medium 24860162
2006 Casc1 knockout mice showed increased susceptibility to chemical induction of lung tumors, establishing a tumor-suppressive role for CASC1 in vivo. Additionally, in vitro colony formation assays showed that the A/J allele of Casc1 produced ~5-6-fold fewer transfectants in human lung cancer cell lines compared to the C57BL/6J allele, indicating allele-specific modulation of cancer cell growth not mediated by apoptosis. Casc1 knockout mouse tumor bioassay; in vitro colony formation assay with allelic variant transfection in human lung cancer cell lines (A549, NCI-H520) Nature genetics / Cancer letters Medium 16458428 16862160
2024 IC97 (the Chlamydomonas ortholog of DNAI7/CFAP94), an intermediate chain of the flagellar dynein IDA f/I1, is required for normal flagellar beat frequency and coordination between the two flagella; loss of IC97 in a Chlamydomonas mutant resulted in slow swimming, low beat frequency, and miscoordination of cis- and trans-flagella, without abolishing phototaxis. Isolation of Chlamydomonas ic97 null mutant; phenotypic analysis of flagellar motility (beat frequency, swimming path, phototaxis); biochemical analysis of IDA f/I1 complex assembly mSphere Medium 39601552

Source papers

Stage 0 corpus · 22 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli. Nature 151 25118175
2006 Candidate lung tumor susceptibility genes identified through whole-genome association analyses in inbred mice. Nature genetics 69 16862160
2018 HCN Regulates Cellular Processes through Posttranslational Modification of Proteins by S-cyanylation. Plant physiology 50 30377236
2021 Hydrogen sulfide: An emerging signaling molecule regulating drought stress response in plants. Physiologia plantarum 35 33860955
2014 Mechanisms promoting escape from mitotic stress-induced tumor cell death. Cancer research 32 24860162
2018 ß-Cyanoalanine Synthase Action in Root Hair Elongation is Exerted at Early Steps of the Root Hair Elongation Pathway and is Independent of Direct Cyanide Inactivation of NADPH Oxidase. Plant & cell physiology 23 29490083
2018 Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1 syndrome. Scientific reports 20 29459759
2013 Properties of capsaicinoids for the control of fungi and oomycetes pathogenic to pepper. Plant biology (Stuttgart, Germany) 18 23452049
2023 A multi-omics analysis identifies molecular features associated with fertility in heifers (Bos taurus). Scientific reports 16 37542054
2024 Mitochondrial ß-Cyanoalanine Synthase Participates in flg22-Induced Stomatal Immunity. Plant, cell & environment 15 39288437
2015 Wounding induces local resistance but systemic susceptibility to Botrytis cinerea in pepper plants. Journal of plant physiology 15 25662842
2008 Association of KRAS polymorphisms with risk for lung adenocarcinoma accompanied by atypical adenomatous hyperplasias. Carcinogenesis 14 18299280
2006 A V141L polymorphism of the human LRMP gene is associated with survival of lung cancer patients. Carcinogenesis 11 16410263
2000 Cloning of a sesquiterpene cyclase and its functional expression by domain swapping strategy. Molecules and cells 11 10850665
2008 Cis-acting genomic elements of the Pas1 locus control Kras mutability in lung tumors. Oncogene 10 18560355
2006 Allelic effects of mouse Pas1 candidate genes in human lung cancer cell lines. Cancer letters 5 16458428
2022 CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study. Computational and mathematical methods in medicine 4 35836922
2023 New Insights on the Role of ß-Cyanoalanine Synthase CAS-C1 in Root Hair Elongation through Single-Cell Proteomics. Plants (Basel, Switzerland) 2 38068690
2013 Induced resistance to Botrytis cinerea in Capsicum annuum by a Fusarium crude elicitor fraction, free of proteins. Plant biology (Stuttgart, Germany) 2 24112636
2026 Organelle-specific hydrogen sulfide metabolism governs redox homeostasis to regulate plant autophagy and cadmium stress resilience. Redox biology 0 42019315
2024 Chlamydomonas IC97, an intermediate chain of the flagellar dynein f/I1, is required for normal flagellar and cellular motility. mSphere 0 39601552
2023 Retracted: CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study. Computational and mathematical methods in medicine 0 38094437

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