Affinage

CDK16

Cyclin-dependent kinase 16 · UniProt Q00536

Length
496 aa
Mass
55.7 kDa
Annotated
2026-04-28
72 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDK16 (PCTAIRE-1) is a cyclin-dependent serine/threonine kinase that functions in vesicular trafficking, cell cycle progression, spindle orientation, autophagy, spermatogenesis, and neuronal development. CDK16 is activated by binding phosphorylated cyclin Y (CCNY or CCNYL1) in a ternary complex with 14-3-3 proteins, where 14-3-3 remodels the cyclin surface to enable CDK engagement, and this activation is antagonized by PKA-mediated phosphorylation of Ser153 which blocks cyclin binding (PMID:22184064, PMID:26205494, PMID:41857027). CDK16 phosphorylates diverse substrates to execute its functions: NSF Ser569 to regulate exocytosis (PMID:16461345), p27 Ser10 to promote its degradation and drive cancer cell proliferation (PMID:25205104), PRC1 Thr481 to control mitotic spindle formation (PMID:30992425, PMID:35449080), KAP0/PRKAR2A Ser83 to couple integrin signaling to spindle orientation (PMID:25605337), and WIPI2B Ser395 (antagonized by PP2A) to regulate autophagosome biogenesis downstream of AMPK (PMID:32098961, PMID:41727099). CDK16 conditional knockout male mice are infertile due to spermatid annulus defects and impaired sperm motility, and CDK16 is required for neuronal dendrite development and neurite outgrowth (PMID:22184064, PMID:21335063).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    The discovery that CDK16 encodes a kinase with a divergent PSTAIRE motif (PCTAIRE) that does not bind p13suc1 established it as a novel CDK subfamily member distinct from classical cell-cycle CDKs.

    Evidence In vitro transcription-translation, p13suc1 binding assay, and immunoprecipitation in heterologous system

    PMID:1437147

    Open questions at the time
    • Enzymatic activity and substrate specificity unknown
    • Cyclin partner unidentified
    • Biological function undefined
  2. 1999 Medium

    Demonstration that endogenous CDK16 is an active kinase in brain and testis with cell-cycle-dependent activity peaking in S/G2 phases, regulated by tyrosine phosphorylation and association with partner proteins including 14-3-3 and p11, resolved the question of whether CDK16 possesses catalytic activity and pointed to a regulated activation mechanism.

    Evidence IP-kinase assays from brain/testis lysates, subcellular fractionation, cell cycle synchronization, yeast two-hybrid and recombinant protein binding

    PMID:10099831 PMID:10511311 PMID:9197417 PMID:9799109

    Open questions at the time
    • Identity of activating cyclin unknown
    • Physiological substrates unidentified
    • 14-3-3 role in activation not defined
  3. 2002 High

    Identification of PKA and CDK5 as upstream kinases—PKA phosphorylating Ser119 (creating a 14-3-3 binding site) and Ser153 (inhibiting kinase activation), and CDK5 phosphorylating Ser95 (enhancing activity)—established a multi-kinase regulatory network controlling CDK16 and explained tissue-specific regulation in brain and muscle.

    Evidence In vitro PKA phosphorylation, mutagenesis, 14-3-3 binding assays, Cdk5 knockout mouse brain/muscle analysis with co-IP

    PMID:12084709 PMID:12154078

    Open questions at the time
    • Cyclin partner still unidentified
    • Substrate specificity undefined
    • Mechanism by which Ser153 phosphorylation inhibits activation unclear
  4. 2005 High

    The findings that CDK16 interacts with COPII component Sec23p and that its kinase activity is required for secretory cargo transport established CDK16's first defined cellular function in vesicular trafficking.

    Evidence Yeast two-hybrid, co-IP, RNAi knockdown, kinase-dead mutant expression, cargo transport assay

    PMID:16091426

    Open questions at the time
    • Direct phosphorylation substrate in COPII pathway not identified
    • Relationship to cyclin-dependent activation unknown
  5. 2006 High

    Identification of NSF as a direct CDK16 substrate phosphorylated at Ser569, with phosphorylation reducing NSF oligomerization and modulating exocytosis, provided the first defined substrate–function link for CDK16.

    Evidence In vitro kinase assay, site-directed mutagenesis (S569A), regulated secretion assay in PC12 cells

    PMID:16461345

    Open questions at the time
    • Whether CDK16-NSF axis operates in vivo (neurons, endocrine cells) not tested
    • Cyclin dependence of this phosphorylation event not established
  6. 2011 High

    The discoveries that cyclin Y is the activating cyclin for CDK16, that PKA-mediated Ser153 phosphorylation blocks this interaction, and that CDK16 conditional knockout mice are male-sterile with spermatid defects solved the longstanding cyclin identity question and defined an essential in vivo function.

    Evidence Co-IP, live imaging, mutagenesis, forskolin treatment, conditional knockout mouse phenotyping with electron microscopy

    PMID:22184064

    Open questions at the time
    • Whether 14-3-3 is required for cyclin Y–CDK16 complex formation not yet resolved
    • CDK16 substrates in spermatogenesis unidentified
  7. 2012 High

    Biochemical definition of CDK16 substrate specificity (proline at +1, basic residue at +4) and quantification of >100-fold activation by cyclin Y, together with identification of BRSK2 as another upstream inhibitory kinase (Ser12), refined the activation mechanism and expanded the regulatory network.

    Evidence Positional scanning peptide library, cyclin Y mutagenesis, BRSK2 co-IP and in vitro kinase assay, insulin secretion assay

    PMID:22796189 PMID:22798068

    Open questions at the time
    • Structural basis of cyclin Y–CDK16 interaction not resolved
    • BRSK2-CDK16 regulation not validated in vivo beyond pancreatic β-cells
  8. 2014 High

    Identification of p27 as a CDK16 substrate (Ser10 phosphorylation promoting degradation) linked CDK16 to cell cycle control and cancer, as CDK16 silencing caused p27 accumulation and mitotic arrest selectively in cancer cells, with epistatic rescue by p27 knockdown.

    Evidence In vitro kinase assay, siRNA epistasis, xenograft tumor model

    PMID:25205104

    Open questions at the time
    • Selectivity for cancer vs. normal cells mechanistically unexplained
    • Whether other CDKs compensate for CDK16 loss in normal cells unknown
  9. 2015 High

    Three advances resolved upstream and downstream mechanisms: cyclin Y requires phosphorylation at Ser100/Ser326 for 14-3-3 binding to activate CDK16 (with patient intellectual-disability variants failing to bind cyclin Y); CCNYL1 was identified as a second activating cyclin essential for male fertility; and KAP0/PRKAR2A Ser83 was identified as a CDK16 substrate linking ECM signaling to spindle orientation.

    Evidence Cell-free reconstitution with phospho-mutants, patient variant analysis, Ccnyl1/Ccny knockout mice, phosphoproteomics with mutagenesis and spindle orientation assay

    PMID:25605337 PMID:26205494 PMID:26305884

    Open questions at the time
    • Structural basis for 14-3-3 requirement in cyclin Y–CDK16 complex not yet determined
    • Kinase(s) phosphorylating cyclin Y Ser100 not identified
  10. 2019 High

    Analog-sensitive CDK16 and chemical genetic screens identified PRC1 (Thr481) and endocytic regulators (AAK1, dynamin 1, synaptojanin 1) as direct substrates, broadening CDK16's functional repertoire to mitotic spindle regulation and synaptic vesicle endocytosis.

    Evidence CRISPR-engineered analog-sensitive kinase, complementary proteomics, mass spectrometry, epistasis in 293T cells, chemical genetic screen in brain extracts

    PMID:30880224 PMID:30992425

    Open questions at the time
    • PRC1 phosphorylation's precise role in spindle assembly vs. cytokinesis not dissected
    • Endocytic substrate phosphorylation not validated in neuronal systems in vivo
  11. 2020 High

    AMPK was identified as the kinase phosphorylating cyclin Y Ser326 to activate CDK16, and the cyclin Y/CDK16 complex was shown to be necessary and sufficient for AMPK-dependent autophagy induction, placing CDK16 as a central effector downstream of the energy-sensing AMPK pathway.

    Evidence Protein microarray, in vitro kinase assay, co-IP, autophagy flux assay, genetic epistasis

    PMID:32098961

    Open questions at the time
    • Direct autophagy substrate of CDK16 downstream of AMPK not identified in this study
    • Tissue-specific relevance of AMPK–CDK16 autophagy axis unexplored
  12. 2022 Medium

    CDK16 was shown to localize to centrosomes, spindle poles, and midbody during mitosis, with knockdown causing aberrant spindle assembly and conferring sensitivity to antimitotic drugs; CDK16–PRC1 phosphorylation was validated as driving TNBC tumor progression and metastasis.

    Evidence Live cell imaging, siRNA, pharmacological inhibition (rebastinib), patient-derived xenograft and organoid models

    PMID:35044463 PMID:35449080

    Open questions at the time
    • Cyclin partner at mitotic structures not determined
    • Selectivity of rebastinib for CDK16 over other kinases limits interpretation
    • Whether CDK16 mitotic function is independent of PRC1 unclear
  13. 2026 High

    Cryo-EM structural determination of the cyclin Y–14-3-3–CDK16 ternary complex revealed that 14-3-3 remodels the CDK-binding surface of cyclin Y and directly contacts the CDK16 activation segment, providing the structural basis for the obligate 14-3-3 requirement; separately, WIPI2B Ser395 was identified as a CDK16 substrate antagonized by PP2A to control neuronal autophagosome biogenesis.

    Evidence Cryo-EM, HDX-MS for ternary complex; in vitro reconstitution with purified enzymes, C. elegans genetic epistasis, primary murine neuron imaging for WIPI2B

    PMID:41727099 PMID:41857027

    Open questions at the time
    • Full-length ternary complex structure not yet available
    • WIPI2B finding from preprint awaits peer review
    • How CDK16 is recruited to autophagosomes versus other cellular sites is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of CDK16 substrates in spermatogenesis, the structural basis for differential use of CCNY versus CCNYL1 in distinct tissues, the mechanism conferring cancer-cell selectivity of CDK16 dependence for p27 degradation, and whether CDK16 has kinase-independent scaffolding functions.
  • Spermatogenesis substrates unidentified
  • CCNY vs CCNYL1 tissue-specific regulation not structurally or genetically resolved
  • No kinase-independent functions tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2 R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9612973 Autophagy 2
Partners
CCNYCCNYL1CDK5NSFPRC1PRKAR2ASEC23AYWHAH
Complex memberships
CCNYL1–CDK16 complexCyclin Y–CDK16–14-3-3 ternary complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CDK16 (PCTAIRE-1) encodes a putative serine/threonine protein kinase with a kinase domain ~50-55% homologous to cdc2/CDC28 family members, containing a cysteine-for-serine substitution in the conserved PSTAIRE motif; recombinant protein failed to bind p13suc1 but was precipitated by anti-cdc2/PSTAIRE antibodies, establishing it as a novel CDK subfamily member. In vitro transcription-translation, p13suc1 binding assay, immunoprecipitation Oncogene High 1437147
1997 PCTAIRE-1 associates with p11 (calpactin I light chain) and 14-3-3 proteins (eta, theta, zeta isoforms), identified by yeast two-hybrid screening of mouse brain cDNA library and confirmed by direct biochemical interaction with pure recombinant proteins. Yeast two-hybrid screening, recombinant protein binding assay Molecular & general genetics Medium 9197417
1999 Pctaire1 kinase activity toward myelin basic protein is associated with the endogenous protein in adult testis and brain, and its activity is regulated through association with regulatory partner(s); two major protein isoforms (~62 and ~68 kDa) are found predominantly in the cytoplasm of terminally differentiated neurons (pyramidal neurons) and elongated spermatids. Immunoprecipitation kinase assay, subcellular fractionation, immunohistochemistry Cell growth & differentiation Medium 10099831
1999 PCTAIRE-1 exhibits cytoplasmic distribution throughout the cell cycle (does not colocalize with cytoskeleton or ER), displays kinase activity toward myelin basic protein requiring binding to a regulatory subunit, and this kinase activity peaks in S and G2 phases and correlates inversely with tyrosine phosphorylation of the molecule. Indirect immunofluorescence, confocal microscopy, in vitro kinase assay, cell cycle synchronization Cell growth & differentiation Medium 10511311
2000 Full interaction of PCTAIRE-1 with p11 and 14-3-3 proteins requires both the N-terminal and C-terminal ends of the protein (not the catalytic core alone); a purified PCTAIRE-1 preparation obtained via p11/14-3-3 affinity resins displayed significant kinase activity, confirming it is an active kinase in brain. Yeast two-hybrid domain mapping, affinity resin purification, immunoprecipitation, in vitro kinase assay European journal of biochemistry Medium 9799109
2000 PCTAIRE-1 shows multiple subcellular localizations in brain neurons: diffuse cytoplasmic distribution in most regions and spot-like localization in nucleoli (co-localizing with B23 protein) of large neurons such as cerebellar Purkinje cells and hippocampal pyramidal cells, suggesting a nucleolar function. Immunolabeling with N-terminal-specific antibody, confocal colocalization with B23 Molecular and cellular neurosciences Medium 11085876
2002 Bacterially expressed PCTAIRE-1 is completely inactive as a kinase but is a good substrate for PKA, which phosphorylates four N-terminal sites; phosphorylation of Ser119 generates a functional 14-3-3 binding site in vitro and in vivo; mutation of Ser153 to alanine generates an activated kinase in transfected mammalian cells comparable to CDK5/p21 activity; gel filtration suggests monomeric PCTAIRE-1 may be the active species in brain. In vitro kinase assay, PKA phosphorylation assay, site-directed mutagenesis, 14-3-3 binding assay, gel filtration of brain extract Journal of cell science High 12154078
2002 Pctaire1 interacts with p35 (the CDK5 regulatory subunit) in vitro and in vivo (in myotubes and skeletal muscle), is phosphorylated by the Cdk5/p25 complex at Ser95 (major site), and Pctaire1 kinase activity is significantly reduced in brain and muscle of Cdk5-null mice, demonstrating CDK5-dependent activation of CDK16. In vitro binding assay, co-immunoprecipitation, in vitro kinase assay with Cdk5/p25, Cdk5 knockout mice Journal of biological chemistry High 12084709
2005 PCTAIRE kinases interact directly with the Sec23p subunit of the COPII complex (identified by two-hybrid screening, direct binding, and immunoprecipitation); inhibition of PCTAIRE kinase activity by kinase-dead mutant or RNAi depletion causes defects in secretory cargo transport, VTC and Golgi localization, establishing a role in early secretory pathway trafficking. Yeast two-hybrid, direct protein binding, co-immunoprecipitation, kinase-dead mutant expression, RNAi knockdown, cargo transport assay Journal of cell science High 16091426
2006 Pctaire1 directly binds and phosphorylates NSF (N-ethylmaleimide-sensitive fusion protein) at Ser569 on its D2 domain; phosphorylation of NSF at S569 reduces its oligomerization, and inhibition of Pctaire1 (via kinase-dead mutant) or expression of NSF-S569A enhances NSF self-association and increases Ca2+-stimulated growth hormone secretion from PC12 cells, establishing a role for CDK16 in regulating exocytosis. Yeast two-hybrid, direct binding, in vitro kinase assay, site-directed mutagenesis, co-immunoprecipitation, regulated secretion assay (PC12 cells) Journal of biological chemistry High 16461345
2010 MRTF-A and MRTF-B (Srf coactivators) regulate Pctaire1 (CDK16) expression, and CDK16 cooperates with Cdk5 in a kinase cascade governing cytoskeletal rearrangements essential for neuronal migration and neurite outgrowth during mouse brain development; conditional deletion of MRTFs dysregulates CDK16 and disrupts multiple brain structures. Conditional gene knockout (mouse), neuronal migration and neurite outgrowth phenotypic analysis, epistasis with Cdk5 pathway Development High 20534669
2011 CDK16 is activated by membrane-associated cyclin Y (CCNY); CCNY binding to CDK16 requires a region upstream of the kinase domain; phosphorylation of CDK16 at Ser153 (potential PKA site) inhibits CCNY binding; CDK16 isolated from murine testis was unphosphorylated at Ser153, interacted with CCNY and exhibited kinase activity; CDK16 conditional knockout male mice are infertile, with spermatozoa showing annulus defects, bent morphology, and impaired motility. Co-immunoprecipitation, GFP-fusion live imaging, PKA activator (forskolin) treatment, site-directed mutagenesis, conditional knockout mouse, spermatozoa motility assay, electron microscopy Molecular and cellular biology High 22184064
2011 Cdk5-dependent phosphorylation of Pctaire1 at Ser95 is required for dendrite development; Pctaire1 is expressed along neurites and concentrated at growth cones of early hippocampal neurons and in dendritic puncta co-localizing with synaptic markers upon maturation; knockdown of Pctaire1 abolishes dendrite development, and phosphorylation-deficient Ser95Ala mutant reduces dendrite complexity. Knockdown (loss-of-function), phospho-deficient mutant expression, live imaging, immunostaining of primary hippocampal neurons Neuroscience Medium 21335063
2012 BRSK2 phosphorylates PCTAIRE1 at Ser12; BRSK2 and PCTAIRE1 interact (yeast two-hybrid, GST pull-down, co-immunoprecipitation) and co-localize in the cytoplasm of MIN6 β-cells; BRSK2-mediated phosphorylation of PCTAIRE1 reduces glucose-stimulated insulin secretion, and BRSK2 knockdown increases serum insulin levels in mice. Yeast two-hybrid, GST pull-down, co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, insulin secretion assay, mouse model Journal of biological chemistry High 22798068
2012 Using positional scanning peptide library technology, PCTAIRE-1 substrate specificity was defined: requires proline at +1 position (like CDKs) but uniquely prefers basic residue at +4 (not +3); a consensus substrate peptide (PCTAIRE-tide) was generated. Cyclin Y binding to PCTAIRE-1 increases kinase activity >100-fold; point mutants of cyclin Y predicted to disrupt binding abolished complex formation and PCTAIRE-1 activation. Positional scanning peptide library, in vitro kinase assay, site-directed mutagenesis of cyclin Y, co-immunoprecipitation Cellular signalling High 22796189
2014 PCTAIRE1 phosphorylates tumor suppressor p27 at Ser10 in vitro; PCTAIRE1 silencing leads to p27 accumulation and S10 dephosphorylation in cancer cells but not nontransformed cells; p27 silencing rescues mitotic arrest caused by PCTAIRE1 knockdown (epistasis); PCTAIRE1 silencing causes aberrant mitosis due to centrosome dynamics defects; CDK16 conditional knockdown suppresses xenograft tumor growth with restored p27 expression. In vitro kinase assay, RNAi, siRNA epistasis, FACS cell cycle analysis, xenograft mouse model Cancer research High 25205104
2014 Pctaire1/Cdk16 promotes skeletal myogenesis by inducing myoblast migration and process formation; overexpression promotes myogenic differentiation and fusion while knockdown inhibits it. Gain- and loss-of-function (overexpression and knockdown), myogenic differentiation assays, migration assays FEBS letters Medium 24931367
2015 PCTK1 regulates integrin-dependent spindle orientation through phosphorylation of Ser83 on KAP0 (regulatory subunit of PKA); this phosphorylation enables KAP0 interaction with myosin X via its FERM domain, which enhances myosin X-FERM association with β1 integrin, constituting a PCTK1-KAP0-myosin X-β1 integrin module linking ECM to spindle orientation. RNAi screen, phosphoproteomic analysis, in vitro kinase assay, co-immunoprecipitation, site-directed mutagenesis, spindle orientation assay Molecular and cellular biology High 25605337
2015 CCNYL1 (Cyclin Y-like 1) interacts with CDK16, and this interaction mutually increases protein stability of both proteins and increases CDK16 kinase activity; N-terminal phosphorylation sites on CDK16 (identified by mass spectrometry) are indispensable for CCNYL1 binding and modulation of CDK16 kinase activity; Ccnyl1 knockout male mice are infertile with impaired sperm motility, while Ccny knockout males are fertile. Knockout mouse (Ccnyl1-/- and Ccny-/-), co-immunoprecipitation, in vitro kinase assay, mass spectrometry phosphorylation site mapping PLoS genetics High 26305884
2015 CDK16 activation requires phosphorylated cyclin Y in complex with 14-3-3: phosphorylation of cyclin Y at Ser100 and Ser326 are required for 14-3-3 binding; recombinant WT cyclin Y (but not S100A/S326A mutant) co-purified with 14-3-3 and activated bacterially expressed PCTAIRE-1 in cell-free assays; CDK16 variants from intellectual disability patients fail to interact with cyclin Y and are inactive. Mass spectrometry phosphorylation site analysis, mutagenesis, cell-free kinase activation assay, patient variant analysis Biochemical journal High 26205494
2017 The first crystal structures of CDK16 kinase domain were determined in complex with indirubin E804 (active-like conformation) and rebastinib (DFG-out inactive conformation), revealing that the ATP-binding pocket accommodates both type I and type II inhibitors; the most potent inhibitors identified were dabrafenib and rebastinib; considerable conformational plasticity was observed, suggesting instability of isolated kinase domain without cyclin partner. X-ray crystallography, cell-free kinase assay, cell-based kinase assay, inhibitor library screening Biochemical journal High 28057719
2017 Dabrafenib inhibits CDK16 activity; CDK16 knockdown inhibits Rb phosphorylation at S780 and increases p27 expression in NRAS- and KRAS-mutant cancer cells, and these effects are phenocopied by dabrafenib but not vemurafenib; CDK16 knockdown was identified by mass spectrometry-based chemical proteomics as a direct dabrafenib target. Mass spectrometry chemical proteomics, siRNA knockdown, immunoblotting, cell proliferation assay Molecular oncology Medium 29112787
2019 CDK16 phosphorylates PRC1 (protein regulator of cytokinesis 1) at Thr481; using analog-sensitive CDK16 generated by CRISPR-Cas9 in 293T cells, specific CDK16 inhibition induced PRC1 dephosphorylation and nuclear delocalization during interphase; CDK16 inhibition and PRC1 downregulation exhibit epistatic effects on cell viability, placing them in the same pathway. Complementary proteomics (substrate identification), analog-sensitive kinase (CRISPR-Cas9), in vitro kinase assay, epistasis by double knockdown Experimental & molecular medicine High 30992425
2019 Chemical genetic screen using engineered PCTAIRE-1/cyclin Y complex with mouse brain extracts identified AAK1, dynamin 1, and synaptojanin 1 as CDK16 substrates involved in receptor endocytosis and synaptic transmission; PCTAIRE-1-dependent phosphorylation sites on AAK1 were identified by mass spectrometry and validated in cellular studies and brain tissue lysates. Chemical genetic screen (in vitro), mass spectrometry, cellular phosphorylation validation, brain tissue lysate analysis Cellular signalling Medium 30880224
2020 AMPK phosphorylates Cyclin Y at Ser326, which promotes its interaction with CDK16 and stimulates CDK16 catalytic activity; the Cyclin Y/CDK16 complex is both sufficient (when overexpressed) and necessary for efficient AMPK-dependent activation of autophagy. Protein microarray (AMPK substrate identification), in vitro kinase assay, co-immunoprecipitation, autophagy flux assay, genetic epistasis Nature communications High 32098961
2021 AKT1 interacts with PCTAIRE1 and stabilizes it (PCTAIRE1 is a substrate of AKT1); LKB1 interacts with PCTAIRE1 and promotes its degradation; BRCA1 also promotes PCTAIRE1 degradation, linking CDK16 protein stability to major cell proliferation/tumor suppression pathways. Co-immunoprecipitation, immunoblotting with kinase active/inactive constructs, overexpression/knockdown experiments Cellular signalling Medium 33932497
2022 PCTAIRE1/CDK16 is a mitotic kinase that localizes at centrosomes during G2, at spindle poles during mitosis, and at the midbody during cytokinesis; CDK16 protein levels peak at mitosis with increased phosphorylation; CDK16 knockdown causes aberrant spindle assembly and chromosome segregation; CDK16 promotes resistance of cancer cells to antimitotic drugs. Live cell imaging (localization), cell cycle synchronization, siRNA knockdown, spindle assembly analysis, antimitotic drug resistance assay Journal of cell science Medium 35044463
2022 CDK16 phosphorylates PRC1 to regulate spindle formation during mitosis in TNBC; genetic knockdown and pharmacological inhibition (rebastinib) of CDK16 suppress TNBC tumor progression and metastasis in cell line-derived xenografts, patient-derived organoids/xenografts, and lung/systemic metastasis mouse models. siRNA knockdown, pharmacological inhibition (rebastinib), xenograft, patient-derived organoid/xenograft, lung metastasis model, transcriptomic analysis Journal of experimental & clinical cancer research Medium 35449080
2026 Cryo-EM and hydrogen/deuterium exchange mass spectrometry revealed that 14-3-3 binding modulates the conformation of the CDK-binding surface of cyclin Y, thereby enabling CDK16 activation; CDK16 interacts with the cyclin box of CCNY while 14-3-3 provides additional contacts including with the CDK16 activation segment; CDK16 activation also requires interactions of CCNY with the N-terminal extension of CDK16. Cryo-EM, hydrogen/deuterium exchange mass spectrometry (HDX-MS), biophysical characterization Nature communications High 41857027
2026 PP2A and CDK16 antagonistically regulate phosphorylation of WIPI2B at Ser395 to control neuronal autophagosome biogenesis; purified mammalian PP2A dephosphorylates and CDK16 phosphorylates WIPI2B S395 in vitro; in C. elegans, PP2A and CDK16 regulate neuronal autophagy through the same genetic pathway as WIPI2B; in primary murine neurons, PP2A and CDK16 colocalize with WIPI2B at autophagosomes, and manipulation of their expression alters autophagosome biogenesis. In vitro reconstitution (purified enzymes), C. elegans genetics (epistasis), primary murine neuron imaging, autophagosome biogenesis assay bioRxivpreprint High 41727099

Source papers

Stage 0 corpus · 72 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Myocardin-related transcription factors regulate the Cdk5/Pctaire1 kinase cascade to control neurite outgrowth, neuronal migration and brain development. Development (Cambridge, England) 104 20534669
1992 PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein kinase gene family. Oncogene 103 1437147
2011 Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis. Molecular and cellular biology 98 22184064
2005 PCTAIRE protein kinases interact directly with the COPII complex and modulate secretory cargo transport. Journal of cell science 84 16091426
1996 X inactivation analysis and DNA methylation studies of the ubiquitin activating enzyme E1 and PCTAIRE-1 genes in human and mouse. Human molecular genetics 72 8852665
2002 Regulation of the CDK-related protein kinase PCTAIRE-1 and its possible role in neurite outgrowth in Neuro-2A cells. Journal of cell science 68 12154078
2006 Pctaire1 phosphorylates N-ethylmaleimide-sensitive fusion protein: implications in the regulation of its hexamerization and exocytosis. The Journal of biological chemistry 58 16461345
2002 Pctaire1 interacts with p35 and is a novel substrate for Cdk5/p35. The Journal of biological chemistry 53 12084709
2014 PCTAIRE1 phosphorylates p27 and regulates mitosis in cancer cells. Cancer research 52 25205104
2016 Lipid Nanoparticle-mediated siRNA Transfer Against PCTAIRE1/PCTK1/Cdk16 Inhibits In Vivo Cancer Growth. Molecular therapy. Nucleic acids 47 27351680
2018 Fisetin decreases TET1 activity and CCNY/CDK16 promoter 5hmC levels to inhibit the proliferation and invasion of renal cancer stem cell. Journal of cellular and molecular medicine 45 30411496
2015 CCNYL1, but Not CCNY, Cooperates with CDK16 to Regulate Spermatogenesis in Mouse. PLoS genetics 45 26305884
1999 The cellular distribution and kinase activity of the Cdk family member Pctaire1 in the adult mouse brain and testis suggest functions in differentiation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 45 10099831
1997 PCTAIRE 2, a Cdc2-related serine/threonine kinase, is predominantly expressed in terminally differentiated neurons. European journal of biochemistry 42 9370357
2012 Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cells. The Journal of biological chemistry 40 22798068
1999 PCTAIRE-1: characterization, subcellular distribution, and cell cycle-dependent kinase activity. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 40 10511311
2017 Dabrafenib inhibits the growth of BRAF-WT cancers through CDK16 and NEK9 inhibition. Molecular oncology 39 29112787
2022 CDK16 promotes the progression and metastasis of triple-negative breast cancer by phosphorylating PRC1. Journal of experimental & clinical cancer research : CR 37 35449080
2017 Structure and inhibitor specificity of the PCTAIRE-family kinase CDK16. The Biochemical journal 37 28057719
2020 AMPK-dependent activation of the Cyclin Y/CDK16 complex controls autophagy. Nature communications 35 32098961
1997 The Cdk-like protein PCTAIRE-1 from mouse brain associates with p11 and 14-3-3 proteins. Molecular & general genetics : MGG 35 9197417
2000 Identification of tudor repeat associator with PCTAIRE 2 (Trap). A novel protein that interacts with the N-terminal domain of PCTAIRE 2 in rat brain. European journal of biochemistry 34 10727952
2019 Phosphoregulation of the oncogenic protein regulator of cytokinesis 1 (PRC1) by the atypical CDK16/CCNY complex. Experimental & molecular medicine 26 30992425
2017 PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle. Journal of dermatological science 26 28274513
2016 Potential role of PCTAIRE-2, PCTAIRE-3 and P-Histone H4 in amyloid precursor protein-dependent Alzheimer pathology. Oncotarget 26 26885753
1998 Characterization of brain PCTAIRE-1 kinase immunoreactivity and its interactions with p11 and 14-3-3 proteins. European journal of biochemistry 26 9799109
2015 PCTK1 regulates integrin-dependent spindle orientation via protein kinase A regulatory subunit KAP0 and myosin X. Molecular and cellular biology 25 25605337
2014 PCTAIRE kinase 3/cyclin-dependent kinase 18 is activated through association with cyclin A and/or phosphorylation by protein kinase A. The Journal of biological chemistry 25 24831015
2006 The regulation of tau phosphorylation by PCTAIRE 3: implications for the pathogenesis of Alzheimer's disease. Neurobiology of disease 25 16766195
1993 The isolation from a unicellular organism, Dictyostelium discoideum, of a highly-related cdc2 gene with characteristics of the PCTAIRE subfamily. Biochimica et biophysica acta 25 8218353
2014 Pctaire1/Cdk16 promotes skeletal myogenesis by inducing myoblast migration and fusion. FEBS letters 24 24931367
2011 Enhanced expression of Pctk1, Tcf12 and Ccnd1 in hippocampus of rats: Impact on cognitive function, synaptic plasticity and pathology. Neurobiology of learning and memory 24 21982980
2014 PCTAIRE1 regulates p27 stability, apoptosis and tumor growth in malignant melanoma. Oncoscience 22 25593992
2011 Cyclin-dependent kinase 5-dependent phosphorylation of Pctaire1 regulates dendrite development. Neuroscience 20 21335063
2000 Multiple subcellular localizations of PCTAIRE-1 in brain. Molecular and cellular neurosciences 20 11085876
2020 circRNA 001306 enhances hepatocellular carcinoma growth by up-regulating CDK16 expression via sponging miR-584-5p. Journal of cellular and molecular medicine 19 33135290
2015 PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines. PloS one 19 25790448
2015 Cyclin Y phosphorylation- and 14-3-3-binding-dependent activation of PCTAIRE-1/CDK16. The Biochemical journal 19 26205494
2012 Analysis of substrate specificity and cyclin Y binding of PCTAIRE-1 kinase. Cellular signalling 19 22796189
2018 CDK16 overexpressed in non-small cell lung cancer and regulates cancer cell growth and apoptosis via a p27-dependent mechanism. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 29674275
2017 Up-regulation of CDK16 by multiple mechanisms in hepatocellular carcinoma promotes tumor progression. Journal of experimental & clinical cancer research : CR 18 28716136
2015 RNA interference screening identifies a novel role for PCTK1/CDK16 in medulloblastoma with c-Myc amplification. Oncotarget 18 25402633
1994 Cloning of genomic loci and chromosomal localization of the human PCTAIRE-1 and -3 protein kinase genes. Genomics 18 8088790
2023 Baicalin Blocks Colon Cancer Cell Cycle and Inhibits Cell Proliferation through miR-139-3p Upregulation by Targeting CDK16. The American journal of Chinese medicine 17 36599649
2021 Lung cancer cells expressing a shortened CDK16 3'UTR escape senescence through impaired miR-485-5p targeting. Molecular oncology 15 34687270
2020 Transcriptomic Analysis in Liquid Biopsy Identifies Circulating PCTAIRE-1 mRNA as a Biomarker in NSCLC. Cancer genomics & proteomics 15 31882554
2023 The roles, molecular interactions, and therapeutic value of CDK16 in human cancers. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 37236028
2021 Proteomic investigation of Cbl and Cbl-b in neuroblastoma cell differentiation highlights roles for SHP-2 and CDK16. iScience 12 33889818
2015 Upregulated CDK16 Expression in Serous Epithelial Ovarian Cancer Cells. Medical science monitor : international medical journal of experimental and clinical research 12 26546806
2016 miR-33a is downregulated in melanoma cells and modulates cell proliferation by targeting PCTAIRE1. Oncology letters 11 27073545
2013 Genetic variation in MKL2 and decreased downstream PCTAIRE1 expression in extreme, fatal primary human microcephaly. Clinical genetics 10 23692340
2004 Cloning and expression analysis of two novel PCTAIRE 3 transcripts from human brain. Gene 10 15019984
2022 LncRNA HCG18 facilitates melanoma progression by modulating miR-324-5p/CDK16 axis. American journal of translational research 9 35273726
2019 Identification of novel PCTAIRE-1/CDK16 substrates using a chemical genetic screen. Cellular signalling 9 30880224
2022 PCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals. Journal of cell science 8 35044463
1996 Expression of alternatively spliced PCTAIRE-1 mRNA in PC12 cells and neonatal rat brain. Gene 8 8918260
2022 Discovery of 3-Amino-1H-pyrazole-Based Kinase Inhibitors to Illuminate the Understudied PCTAIRE Family. International journal of molecular sciences 7 36499165
2020 New tricks of an old autophagy regulator: AMPK-dependent regulation of autophagy through CCNY (cyclin Y)-CDK16. Autophagy 7 32401167
1998 UHX1 and PCTK1: precise characterisation and localisation within a gene-rich region in Xp11.23 and evaluation as candidate genes for retinal diseases mapped to Xp21.1-p11.2. European journal of human genetics : EJHG 6 9801870
2021 Regulation of PCTAIRE1 protein stability by AKT1, LKB1 and BRCA1. Cellular signalling 5 33932497
1995 Physical linkage of the cdc2-related gene (PCTK1) and the ubiquitin-activating enzyme E1 gene (UBE1) on human Xp11.3. Cytogenetics and cell genetics 5 7656587
2021 Long non-coding RNA TPT1-AS1 alleviates cell injury and promotes the production of extracellular matrix by targeting the microRNA-324-5p/CDK16 axis in human dermal fibroblasts after thermal injury. Experimental and therapeutic medicine 3 34149889
2025 CDK16+ Luminal Progenitor Cell-Like Tumor Cells Interacted with POSTN+ Cancer-Associated Fibroblasts Associate with Chemo-Resistance In Breast Cancer. Small methods 2 39930931
2023 PCTAIRE Protein Kinase 1 (PCTK1) Suppresses Proliferation, Stemness, and Chemoresistance in Colorectal Cancer through the BMPR1B-Smad1/5/8 Signaling Pathway. International journal of molecular sciences 1 37373155
2019 Retraction Note: Up-regulation of CDK16 by multiple mechanisms in hepatocellular carcinoma promotes tumor progression. Journal of experimental & clinical cancer research : CR 1 31122280
2005 Generation and characterization of monoclonal antibodies to human PCTAIRE 3. Hybridoma (2005) 1 15857174
2026 Single-cell RNA-Seq reveals transcriptional heterogeneity in sepsis and down-regulation of SNHG5/miR-324-5p/CDK16 axis in T cells. Cell biology and toxicology 0 41673232
2026 PP2A and CDK16 antagonistically regulate WIPI2B phosphorylation and neuronal autophagosome biogenesis. bioRxiv : the preprint server for biology 0 41727099
2026 Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16. Nature communications 0 41857027
2026 Computer-aided discovery of CDK16 inhibitors: a docking-augmented machine learning regression modelling approach. Journal of computer-aided molecular design 0 41940903
2025 Copper orchestrates triple-negative breast cancer progression via the STEAP3-dependent CDK16-JAK1 activation. Cancer letters 0 41338444
2024 UBA1-CDK16 : A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism. bioRxiv : the preprint server for biology 0 38405903