Affinage

CDK11B

Cyclin-dependent kinase 11B · UniProt P21127

Length
795 aa
Mass
92.6 kDa
Annotated
2026-04-28
28 papers in source corpus 18 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CDK11B encodes a cyclin-dependent kinase that produces two major isoforms—CDK11(p110) and CDK11(p58)—with distinct roles in transcription-coupled splicing, mitotic progression, and translational control. CDK11(p110) resides in complexes with RNA polymerase II and splicing factors to couple transcription with pre-mRNA splicing, an activity regulated by CHK2-mediated phosphorylation at S737 that promotes homodimerization (PMID:15060143, PMID:23178491); CDK11(p110) also directly binds gene promoters such as CBFβ to activate transcription (PMID:31610798). The mitotic isoform CDK11(p58), translated via an IRES element repressed by PTB (PMID:22037210), autophosphorylates at Thr-370 to enable dimerization and kinase activity (PMID:21078675), and executes multiple mitotic functions: it recruits Bub1 and Shugoshin 1 to protect centromeric cohesion (PMID:17606997, PMID:24436071), interacts with Plk4 to drive centriole duplication (PMID:21297952), forms a complex with cyclin L1β to promote ESCRT-III–dependent abscission opposing Aurora B (PMID:31653703), and phosphorylates eIF3F to repress cap-dependent translation during M phase (PMID:32030451). CDK11-null mice die at the blastocyst stage from proliferative failure and mitotic arrest, establishing the essential requirement for these kinases in cell viability (PMID:15060143).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 High

    Establishing that CDK11 is essential for viability resolved whether the two paralogous CDK11 loci are redundant: knockout of CDK11(p110/p58) causes blastocyst-stage lethality with mitotic arrest and apoptosis, demonstrating a non-redundant requirement in cell proliferation and survival.

    Evidence Homologous recombination knockout in mice with phenotypic analysis of null embryos

    PMID:15060143

    Open questions at the time
    • Whether CDK11A can partially compensate for CDK11B loss was not tested
    • Specific mitotic substrates responsible for arrest not identified
  2. 2004 Medium

    Biochemical isolation of CDK11(p110) in complexes with RNA pol II and splicing factors established a molecular framework for how this isoform couples transcription to pre-mRNA splicing.

    Evidence Biochemical complex purification and fractionation from mammalian cells

    PMID:15060143

    Open questions at the time
    • Direct substrates within the spliceosome not identified
    • No reconstitution of splicing stimulation with purified components
  3. 2007 High

    Demonstrating that CDK11(p58) depletion causes premature sister chromatid separation with altered Shugoshin 1 localization established its role as a protector of centromeric cohesion during mitosis, a function not rescued by co-depletion of Plk1 or Sgo1.

    Evidence Hypomorphic siRNA knockdown with epistasis rescue experiments; fluorescence microscopy in human cells

    PMID:17606997

    Open questions at the time
    • Whether CDK11(p58) directly phosphorylates Sgo1 or Bub1 was not determined
    • Cyclin partner for cohesion function not identified
  4. 2010 High

    Identification of Thr-370 autophosphorylation as the switch for CDK11(p58) homodimerization and catalytic activation resolved how the kinase is activated, since T370A mutants lost all downstream functions including apoptosis induction and transcriptional repression.

    Evidence In vitro kinase assay with T370A/T370D/D224N site-directed mutants, Co-IP for dimerization, functional assays

    PMID:21078675

    Open questions at the time
    • Structural basis of dimerization interface unknown
    • Whether Thr-370 phosphorylation is regulated by an upstream signal in vivo not established
  5. 2011 High

    Showing that CDK11(p58) interacts with Plk4 and is required for centrosomal recruitment of Plk4 and Cep192 extended its mitotic role to centriole duplication, a function upstream of Plk4-driven centriole biogenesis.

    Evidence Co-IP of CDK11(p58) with Plk4, siRNA depletion, Plk4 overexpression rescue in multiple cell lines

    PMID:21297952

    Open questions at the time
    • Whether CDK11(p58) phosphorylates Plk4 directly not tested
    • Temporal regulation of the CDK11–Plk4 interaction during the cell cycle not mapped
  6. 2011 Medium

    Discovery that PTB directly binds the CDK11(p58) IRES and represses its translation in ES cells provided the first trans-acting regulator of isoform-specific CDK11(p58) production, explaining how CDK11(p58) levels are restricted to G2/M.

    Evidence RNA immunoprecipitation, IRES reporter assay, PTB knockout embryonic stem cells

    PMID:22037210

    Open questions at the time
    • Whether PTB regulation operates in somatic mitotic cells not confirmed
    • Other IRES trans-acting factors not identified
  7. 2012 High

    Identification of CHK2 as the kinase that phosphorylates CDK11(p110) at S737 to promote dimerization and splicing activity resolved how the transcription-coupled splicing function of the p110 isoform is regulated, independently of DNA damage.

    Evidence Tandem affinity purification, in vitro kinase assay, S737A mutagenesis, pre-mRNA splicing assay, CHK2 knockdown/overexpression

    PMID:23178491

    Open questions at the time
    • In vivo splicing targets affected by the CHK2–CDK11 axis not catalogued
    • Physiological stimulus that activates this DNA damage-independent CHK2 pathway unknown
  8. 2014 High

    Kinase-dead rescue experiments established that CDK11(p58) catalytic activity—not merely its presence—is required for Bub1 and Sgo1 centromeric recruitment and cohesion protection specifically in mitosis, not G2.

    Evidence siRNA depletion with kinase-dead mutant rescue, immunofluorescence of Bub1, Sgo1, H3K4me2 in human cells

    PMID:24436071

    Open questions at the time
    • Direct phosphorylation substrate linking CDK11 to Bub1/Sgo1 recruitment not identified
  9. 2019 High

    ChIP and EMSA demonstration that CDK11(p110) directly binds the CBFβ promoter and activates its transcription revealed a direct transcription factor-like activity for CDK11, beyond its known kinase and splicing functions.

    Evidence ChIP, EMSA, luciferase promoter assay in osteosarcoma cells

    PMID:31610798

    Open questions at the time
    • Whether promoter binding requires kinase activity or a cyclin partner not tested
    • Genome-wide scope of CDK11(p110) promoter occupancy unknown
  10. 2019 High

    Identifying a CDK11(p58)–cyclin L1β complex at the intercellular bridge that promotes ESCRT-III assembly for abscission, opposing Aurora B, revealed a new post-anaphase function for CDK11(p58) in cytokinesis completion.

    Evidence Co-IP, live-cell imaging, siRNA depletion, kinase-dead rescue, Aurora B inhibitor epistasis

    PMID:31653703

    Open questions at the time
    • Direct substrate phosphorylated by CDK11(p58)–cyclin L1β to trigger ESCRT-III assembly not identified
    • Whether this opposes the NoCut checkpoint directly unknown
  11. 2020 High

    Demonstration that CDK11(p58) phosphorylates eIF3F during M phase to repress cap-dependent translation identified the first mechanism by which a CDK directly links mitotic entry to global translational repression.

    Evidence In vitro kinase assay, eIF3F phosphosite mutagenesis, cap-dependent translation reporter

    PMID:32030451

    Open questions at the time
    • Whether eIF3F phosphorylation also affects IRES-dependent translation not addressed
    • In vivo validation of specific phosphosites during endogenous mitosis not shown
  12. 2022 Medium

    Identification of MRPS23 S11 as a CDK11/cyclin D3 phosphosite that activates PI3K-AKT signaling in breast cancer expanded the substrate repertoire of CDK11(p58) beyond canonical mitotic and splicing targets.

    Evidence In vitro kinase assay with CDK11/cyclin D3, MALDI-ToF/ToF mass spectrometry, S11A/S11G mutagenesis

    PMID:35962848

    Open questions at the time
    • Physiological context of MRPS23 phosphorylation during the cell cycle not established
    • Mechanism connecting mitochondrial ribosomal protein phosphorylation to PI3K-AKT unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the direct substrates that mediate CDK11(p58)'s cohesion-protection and centriole-duplication functions, the structural basis of CDK11 dimerization, and the degree of functional overlap between CDK11A and CDK11B paralogs.
  • No crystal structure of CDK11 or CDK11–cyclin complex available
  • Direct phosphorylation targets for cohesion and centrosome functions unidentified
  • CDK11A vs CDK11B paralog-specific functions not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0003677 DNA binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 6 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-392499 Metabolism of proteins 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
B4GALT1BUB1CCND3CCNL1CHEK2EIF3FPLK4SGO1
Complex memberships
CDK11(p58)–cyclin D3 complexCDK11(p58)–cyclin L1β abscission complexRNA pol II / splicing factor complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CDK11(p110/p58)-null mice die at the blastocyst stage (E3.5) due to apoptosis, with cells showing both proliferative defects and mitotic arrest, establishing that CDK11 kinases are essential for cellular viability and early embryonic development. Homologous recombination knockout in mice; phenotypic analysis of null embryos Molecular and cellular biology High 15060143
2004 CDK11(p110) is part of large-molecular-weight complexes containing RNA polymerase II, transcriptional elongation factors, and general pre-mRNA splicing factors, suggesting it couples transcription and pre-mRNA splicing. Biochemical complex purification/fractionation Molecular and cellular biology Medium 15060143
2007 CDK11(p58) is required for sister chromatid cohesion and completion of mitosis; its depletion causes misaligned/lagging chromosomes, premature sister chromatid separation, altered Shugoshin 1 (Sgo1) localization, and premature dissociation of cohesin complexes. This severe phenotype was rescued by CDK11(p58) but not by co-depletion with Plk1 or Sgo1. Hypomorphic siRNA knockdown with epistasis rescue experiments; fluorescence microscopy of chromosome behavior Journal of cell science High 17606997
2011 CDK11(p58) is required for centriole duplication; its depletion reduces centrosomal recruitment of Plk4 and Cep192 during mitosis. CDK11(p58) directly interacts with Plk4, and centrioles from CDK11-depleted cells cannot be over-duplicated following Plk4 overexpression. siRNA knockdown, Co-IP (CDK11(p58) with Plk4), immunofluorescence of centrosomal proteins, Plk4 overexpression rescue assay PloS one High 21297952
2012 CHK2 kinase phosphorylates CDK11(p110) at serine 737 in vitro in a DNA damage-independent manner; this phosphorylation promotes CDK11(p110) homodimerization and is required for its splicing-activating activity. CHK2 overexpression promotes pre-mRNA splicing, and mutation of S737 to alanine abrogates CDK11(p110) splicing activity. Tandem affinity purification, in vitro kinase assay, site-directed mutagenesis (S737A), pre-mRNA splicing assay, CHK2 knockdown/overexpression Oncogene High 23178491
2010 CDK11(p58) autophosphorylates at Thr-370, and this autophosphorylation is required for homodimerization and kinase activity. The kinase-dead mutant D224N fails to form homodimers. T370A mutant cannot dimerize or be phosphorylated by wild-type CDK11(p58), loses kinase activity, fails to repress androgen receptor transactivation, and cannot enhance apoptosis. In vitro kinase assay, site-directed mutagenesis (T370A, T370D, D224N), Co-IP for dimerization, transactivation assay, apoptosis assay The Journal of biological chemistry High 21078675
2014 CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres during mitosis. CDK11 depletion prevents Bub1 and Shugoshin 1 recruitment to centromeres; a kinase-dead version of CDK11(p58) fails to rescue CDK11 depletion-induced sister chromatid separation. Loss of cohesion occurs in mitosis but not G2. siRNA depletion, kinase-dead mutant rescue, immunofluorescence of Bub1, Sgo1, and histone H3K4me2 Chromosome research High 24436071
2019 CDK11p58 forms a complex with cyclin L1β during late cytokinesis and localizes to the stem body (intercellular bridge). CDK11p58 kinase activity is required for ESCRT-III filament formation at the abscission site and for completion of abscission; this activity opposes Aurora B kinase to enable abscission. Co-immunoprecipitation, live-cell imaging/immunofluorescence, siRNA depletion, kinase-dead rescue, Aurora B inhibitor epistasis The Journal of biological chemistry High 31653703
2020 CDK11/p58 phosphorylates eIF3F (a subunit of the eIF3 translation initiation complex) during M phase, repressing cap-dependent translation. Knockdown of CDK11/p58 abolishes M phase translational repression; alanine substitution of CDK11/p58 target sites in eIF3F nullifies cell cycle-dependent translational regulation. Ectopic expression/knockdown of CDK11/p58, in vitro phosphorylation assay, site-directed mutagenesis of eIF3F phosphorylation sites, cap-dependent translation reporter assay Cellular and molecular life sciences High 32030451
2020 B4GALT1 (beta-1,4-galactosyltransferase 1) interacts with and stabilizes CDK11p110 via N-linked glycosylation, promoting cancer progression and chemoresistance. Elevated NF-κB p65 activity transcriptionally upregulates B4GALT1, forming a p65-B4GALT1-CDK11p110 signaling axis. Co-IP, glycosylation inhibition assay, genetic knockdown/overexpression, orthotopic PDAC xenograft model Cancer letters Medium 33309857
2005 CDK11(p58)-mediated apoptosis (enhanced by cycloheximide treatment) involves cytochrome c release, caspase-3 activation, and subsequent caspase-3 cleavage of CDK11(p58) itself. Beta-1,4-galactosyltransferase 1 (beta1,4-GT1) promotes this apoptotic pathway, and its knockdown inhibits it. siRNA knockdown of beta1,4-GT1, caspase-3 cleavage assay, cytochrome c release assay, flow cytometry Biochemical and biophysical research communications Medium 15629159
2007 CDK11(p58) down-regulates Bcl-2 expression and its Ser70/Ser87 phosphorylation during cycloheximide-induced apoptosis; overexpression of Bcl-2 counteracts CDK11(p58) pro-apoptotic activity. Kinase activity of CDK11(p58) is essential for Bcl-2 down-regulation and apoptosis induction. Ectopic overexpression, kinase-dead mutant, western blot, apoptosis assay Molecular and cellular biochemistry Medium 17516030
2010 Cyclin D3 interacts with CDK11(p58), and the cyclin D3/CDK11(p58) complex localizes primarily to the nucleus, where it represses Schwann cell proliferation and induces apoptosis. Silencing cyclin D3 reverses CDK11(p58)-mediated proliferation repression. Co-IP, immunofluorescence localization, siRNA silencing, overexpression, proliferation/apoptosis assays Inflammation Medium 20066559
2011 Polypyrimidine tract-binding protein (PTB) directly binds to the IRES region of CDK11(p58) mRNA and represses its IRES-dependent translation in embryonic stem cells. Loss of PTB leads to elevated CDK11(p58) protein and prolonged G2/M phase. RNA immunoprecipitation, IRES reporter assay, PTB knockout ES cells, proliferation analysis Cell cycle Medium 22037210
2019 CDK11p110 (but not CDK11p58) directly binds the CBFβ gene promoter and transcriptionally activates CBFβ expression in osteosarcoma cells. CDK11p110-dependent CBFβ upregulation promotes osteosarcoma cell proliferation. Promoter luciferase assay, chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA/Gel Shift), gene array Cell communication and signaling High 31610798
2020 CDK11B promotes ubiquitin-proteasome-mediated degradation of the transcription factor SPDEF in hepatocellular carcinoma stem cells. SPDEF degradation relieves its suppression of miR-448, which in turn represses DOT1L, promoting HCC stem cell self-renewal. Co-IP, ubiquitination-IP, ChIP assay, sphere/colony formation assay, in vivo xenograft Cancer gene therapy Medium 33328586
2022 CDK11-p58 (referred to as CDK11A isoform in this study but confirmed as CDK11 p58 isoform) phosphorylates MRPS23 at serine 11, as shown by in vitro kinase assay and MALDI-ToF/ToF analysis. MRPS23 S11 phosphorylation activates PI3K-AKT and anti-apoptotic pathways to promote breast cancer cell proliferation. Co-IP, phosphoprotein enrichment, in vitro kinase assay with CDK11/cyclin D3, MALDI-ToF/ToF mass spectrometry, site-directed mutagenesis (S11A/S11G) Molecular biology reports Medium 35962848
2011 CDK11(p58) activates p38 and JNK MAPK pathways in astrocytes upon LPS stimulation, promoting inflammatory response. CDK11(p58) knockdown reduces LPS-induced inflammatory response, and overexpression enhances it. siRNA knockdown, overexpression, western blot of p38 and JNK phosphorylation, LPS stimulation assay Neurochemical research Low 22120654
2015 CDK11(p58) inhibits VEGF transcription and promoter activity in breast cancer cells in a kinase-activity-dependent manner, thereby suppressing angiogenesis both in vitro and in vivo in nude mice. Kinase-dead CDK11(p58) fails to inhibit VEGF mRNA or promoter activity. Dual-luciferase reporter for VEGF promoter, real-time PCR, kinase-dead mutant, xenograft tumor model, immunohistochemistry BMC cancer Medium 26470709

Source papers

Stage 0 corpus · 28 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Failure to proliferate and mitotic arrest of CDK11(p110/p58)-null mutant mice at the blastocyst stage of embryonic cell development. Molecular and cellular biology 75 15060143
2007 CDK11(p58) is required for the maintenance of sister chromatid cohesion. Journal of cell science 70 17606997
2015 Cyclin-dependent kinase 11(p110) (CDK11(p110)) is crucial for human breast cancer cell proliferation and growth. Scientific reports 53 25990212
1998 Duplication of a genomic region containing the Cdc2L1-2 and MMP21-22 genes on human chromosome 1p36.3 and their linkage to D1Z2. Genome research 51 9750192
2020 Galactosyltransferase B4GALT1 confers chemoresistance in pancreatic ductal adenocarcinomas by upregulating N-linked glycosylation of CDK11p110. Cancer letters 40 33309857
2011 CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes. PloS one 30 21297952
2012 CHK2 kinase promotes pre-mRNA splicing via phosphorylating CDK11(p110). Oncogene 26 23178491
2005 Downregulation of beta1,4-galactosyltransferase 1 inhibits CDK11(p58)-mediated apoptosis induced by cycloheximide. Biochemical and biophysical research communications 24 15629159
2011 Polypyrimidine tract-binding protein regulates the cell cycle through IRES-dependent translation of CDK11(p58) in mouse embryonic stem cells. Cell cycle (Georgetown, Tex.) 22 22037210
2019 CDK11p110 plays a critical role in the tumorigenicity of esophageal squamous cell carcinoma cells and is a potential drug target. Cell cycle (Georgetown, Tex.) 18 30722725
2010 Thr-370 is responsible for CDK11(p58) autophosphorylation, dimerization, and kinase activity. The Journal of biological chemistry 17 21078675
2017 DNA methylation of the CDC2L1 gene promoter region decreases the expression of the CDK11p58 protein and reduces apoptosis in keloid fibroblasts. Archives of dermatological research 16 29204684
2014 CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 16 24436071
2015 Critical role of CDK11(p58) in human breast cancer growth and angiogenesis. BMC cancer 15 26470709
2007 CDK11(p58) protein kinase activity is associated with Bcl-2 down-regulation in pro-apoptosis pathway. Molecular and cellular biochemistry 15 17516030
2020 Involvement of CDK11B-mediated SPDEF ubiquitination and SPDEF-mediated microRNA-448 activation in the oncogenicity and self-renewal of hepatocellular carcinoma stem cells. Cancer gene therapy 13 33328586
2019 Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation. Cell communication and signaling : CCS 13 31610798
2010 Cyclin D3/CDK11(p58) complex involved in Schwann cells proliferation repression caused by lipopolysaccharide. Inflammation 11 20066559
2019 CDK11p58-cyclin L1β regulates abscission site assembly. The Journal of biological chemistry 10 31653703
2002 Analysis of mutations and identification of several polymorphisms in the putative promoter region of the P34CDC2-related CDC2L1 gene located at 1P36 in melanoma cell lines and melanoma families. International journal of cancer 10 12115485
2020 A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis. Cellular and molecular life sciences : CMLS 9 32030451
2013 LPS-stimulating astrocyte-conditioned medium causes neuronal apoptosis via increasing CDK11(p58) expression in PC12 cells through downregulating AKT pathway. Cellular and molecular neurobiology 9 23703121
2011 CDK11(p58) promotes rat astrocyte inflammatory response via activating p38 and JNK pathways induced by lipopolysaccharide. Neurochemical research 8 22120654
2022 Mitochondrial ribosomal small subunit (MRPS) MRPS23 protein-protein interaction reveals phosphorylation by CDK11-p58 affecting cell proliferation and knockdown of MRPS23 sensitizes breast cancer cells to CDK1 inhibitors. Molecular biology reports 6 35962848
2011 Analyses of CDC2L1 gene mutations in keloid tissue. Clinical and experimental dermatology 5 22188294
2004 Isolation and characterization of the human Cdc2L1 gene promoter. Gene 5 15656972
1996 Analysis of location and integrity of the human PITSLRE (p58(cdc2L1)) genes in neuroblastoma cell genomes. International journal of oncology 4 21544474
2019 Correction to: Transcriptional activation of CBFβ by CDK11p110 is necessary to promote osteosarcoma cell proliferation. Cell communication and signaling : CCS 1 31665012