Biomarker: CDK6

Histology type: endometrial carcinoma

Country: Japan

Region: Tokyo

Followed up time :

Conclusion: CDK4/6-specific activity can be used as a biomarker to predict prognosis and, possibly, chemo-sensitivity. The combination of Ki-67 expression might strengthen the clinical usefulness of CDK4/6SA as a biomarker.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : high CDK4/6SA (>3.0)

Expression elevation: The extent of CDK4 expression was scored as follows: 0 (0%), 1+ (0–5%), 2+ (5–50%), and 3+ (>50%) along with the previous study (Shiozawa et al, 1997).

Statictics: cutoff<60;cutoff>60

Cohort age: 68;41

Funtion Uniprot: Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663).

UniProt ID: Q00534

UniProt Link: https://www.uniprot.org/uniprotkb/Q00534/entry

Biological function from UniProt: #Cell cycle #Cell division #Differentiation

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells.

Subcellular UniProt: #Cell projection #Cytoplasm #Cytoskeleton #Nucleus

Alternative name from UniProt:

Miscellaneous: Over-expressed in some leukemias and malignancies (including sarcoma, glioma, breast tumors, lymphoma and melanoma) as a consequence of nearby translocations. Enhances beta-cells engraftment in pancreatic islets of Langerhans of diabetic patients.

Catalytic activity: ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein];ATP + L-threonyl-[protein] = ADP + H+ + O-phospho-L-threonyl-[protein];

Activity regulation: Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast

Gene name from HGNC: CDK6 (PLSTIRE)

HPA class: Cancer-related genes Disease related genes Enzymes FDA approved drug targets Human disease related genes Metabolic proteins Plasma proteins

AlphaFold DB: Q00534

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q00534

Induction: Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry.

HPA link: https://www.proteinatlas.org/ENSG00000105810-CDK6

Tissue specificity RNA from HPA: Tissue enhanced (lymphoid tissue)

Tissue expression from HPA: Cytoplasmic expression in several tissues, which in cases was combined with nuclear expression. Highest expression in bone marrow cells.

Single cell type specificity Cell type enhanced (Late spermatids, Oligodendrocytes, Early spermatids, Erythroid cells)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Cytosol (Single cell variability)

Cancer prognostic summary HPA Prognostic marker in pancreatic cancer (unfavorable) and urothelial cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000105810-CDK6/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000105810-CDK6/pathology/endometrial+cancer

Survival figure legend: Prognostic impact of CDK4/6SA alone and in combination with Ki-67 expression.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815892/figure/fig2/

Phenotype ID: 616080

Disease: Microcephaly 12, primary, autosomal recessive (MCPH12);

Note1: The disease is caused by variants affecting the gene represented in this entry

OMIM: 603368

OMIM link1: https://www.omim.org/entry/616080

OMIM link2: https://www.omim.org/entry/603368;https://www.omim.org/entry/612223;

Phenotype: 612223

HGNC ID: HGNC:1777

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1777