Biomarker: CDK4

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: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.

UniProt ID: P11802

UniProt Link: https://www.uniprot.org/uniprotkb/P11802/entry

Biological function from UniProt: #Cell cycle #Cell division

Molecular function from UniProt:

Subcellular UniProt: #Cytoplasm #Membrane #Nucleus

Alternative name from UniProt:

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: Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequent activation.

Recommended name: Cyclin-dependent kinase 4

Gene name from HGNC: CDK4 (PSK-J3)

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

AlphaFold DB: P11802

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P11802

HPA link: https://www.proteinatlas.org/ENSG00000135446-CDK4

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Mainly nuclear but also cytoplasmic expression at variable levels in most tissues.

Single cell type specificity Non-specific - Basic cellular processes (mainly)

Immune cell specificity: Low immune cell specificity

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

Cancer prognostic summary HPA Prognostic marker in liver cancer (unfavorable) and renal cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000135446-CDK4/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000135446-CDK4/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: 609048;

Disease: Melanoma, cutaneous malignant 3 (CMM3)

Note1: Disease susceptibility is associated with variants affecting the gene represented in this entry

OMIM: 123829

OMIM link1: https://www.omim.org/entry/609048

OMIM link2: https://www.omim.org/entry/123829

HGNC ID: HGNC:1773

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1773