Recombinant Human Cyclin-Dependent Kinase 4 (CDK4) Protein (His)

Name: Recombinant Human Cyclin-Dependent Kinase 4 (CDK4) Protein (His)
Brand: Beta LifeScience
SKU: BLC-04040P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

Collections: All products, High-quality recombinant proteins, Other recombinant proteins

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Product Overview

Description	Recombinant Human Cyclin-Dependent Kinase 4 (CDK4) Protein (His) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	P11802
Target Symbol	CDK4
Synonyms	Cdk 4; cdk4; CDK4 protein; CDK4_HUMAN; Cell division kinase 4; Cell division protein kinase 4; CMM 3; CMM3; Crk3; Cyclin dependent kinase 4; Cyclin-dependent kinase 4; Melanoma cutaneous malignant 3; MGC14458; p34 cdk4; PSK J3; PSK-J3
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-6His
Target Protein Sequence	ATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEGNPE
Expression Range	2-303aa
Protein Length	Full Length of Mature Protein
Mol. Weight	37.6kDa
Research Area	Cell Cycle
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	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 G(1)/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 G(1) phase. Hypophosphorylates RB1 in early G(1) 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.
Subcellular Location	Cytoplasm. Nucleus. Nucleus membrane.
Protein Families	Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily
Database References	HGNC: 1773 OMIM: 123829 KEGG: hsa:1019 STRING: 9606.ENSP00000257904 UniGene: PMID: 29228296 MiR-340 overexpression inhibited tumor growth by regulating CDK4 expression. miR-340 functions as a tumor suppressor in non small cell lung cancer (NSCLC) cells and may provide a potential target of NSCLC treatment. PMID: 29935356 CDK4 and XPO1 are not altered in a rare undifferentiated sarcoma, making them therapeutic targets PMID: 27329820 while mTOR inhibitors restore endocrine sensitivity, CDK4/6 inhibitors may favor the emergence of estrogen receptor 1 (ESR1) mutations resulting in ligand-independent activity of the receptor PMID: 28685610 Inhibition of CDK4/6 is potentially a highly effective strategy for the treatment of SHH and MYC-amplified group 3 medulloblastoma. PMID: 28637687 SOX12 can increase the expression of CDK4 and IGF2BP1, which confer malignant phenotypes to Hepatocellular Carcinoma. PMID: 28975985 Study showed that CDK4 and BCAS2 may be target genes of miR-486 and levels of CDK4 and BCAS2 were both significantly higher in the esophageal cancer tissues and cell lines than levels in the normal tissues and cells. PMID: 29115564 blocking CDK4 activity efficiently eliminated both normal and chemotherapy-resistant cancer cells in triple negative breast cancers, highlighting CDK4 as a promising novel therapeutic target for these aggressive breast tumors. PMID: 27759034 Amplification of gene CDK4 is associated with lung adenocarcinoma. PMID: 28381877 Ongoing trials of doublet and triplet targeted therapies containing ribociclib seek to identify optimal CDK4/6-based targeted combination regimens for various tumor types and advance the field of precision therapeutics in oncology PMID: 28351928 Palbociclib induces activation of AMPK and inhibits hepatocellular carcinoma in a CDK4/6-independent manner PMID: 28453226 The combination of ribociclib, a dual inhibitor of cyclin-dependent kinase (CDK) 4 and 6, and the ALK inhibitor ceritinib demonstrated higher cytotoxicity and synergy scores (P = 0.006) in cell lines with ALK mutations as compared with cell lines lacking mutations or alterations in ALK . PMID: 27986745 Results showed that CDK4 expression was up-regulated in colorectal carcinoma and suggested that cdc37 increased the stability of CDK4 to activate RB1 which ultimately promotes G1-S transition. PMID: 29288563 Data show that sulfatase 1 (hSulf-1) overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting cyclin dependent kinase 4 (CDK4) nuclear import. PMID: 27806323 we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. PMID: 27662657 CDK4/6 inhibition suppressed cell cycle progression of ER+/HER2- brreast cancer models. PMID: 27564114 Proliferating tumor stem cells with high telomerase expression are suitable targets for CDK4/6 inhibitor, palbociclib. PMID: 28039467 PRMT5 inhibited the interaction between CDK4 and CDKN2A and then activated the CDK4-RB-E2F pathway in hepatocellular carcinoma cells under glucose induction. PMID: 27708221 This is the first clinical study exploring the use of a CDK4/6 inhibitor in a pediatric population. In this phase I study, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of single-agent ribociclib in pediatric patients with neuroblastoma, MRTs, or other cancers with documented cyclin D-CDK4/6-INK4-retinoblastoma pathway aberrations PMID: 28432176 Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth. PMID: 27542767 network-based rigidity analysis and emulation of thermal unfolding of the Cdk4-cyclin D complex and Hsp90-Cdc37-Cdk4 complex revealed weak spots of kinase instability that are present in the native Cdk4 structure and are targeted by the chaperone during client recruitment PMID: 29267381 The study of 140 cases confirms that the incidence of MDM2/CDK4 amplification is low (5%) in large and/or deep-seated (subfascial) lipomatous neoplasms with histological features of a lipoma (or lipoma variant). PMID: 27020493 miR-486-5p inhibits non-small cell lung cancer progression by down-regulating the expression of CDK4. PMID: 27049724 Combined PI3Kalpha and CDK4/6 inhibition significantly improved disease control in human xenograft models compared with either monotherapy. PMID: 28947417 High amplification levels of CDK4 is associated with dedifferentiated liposarcoma. PMID: 29153098 Activation of cdk4 triggers NAFLD. PMID: 27373160 Our results show that combined exogenous expression of hTERT and mutant CDK4 is an effective method to generate single-cell-derived Cancer-associated fibroblasts (CAFs) clones. This provides an innovative and suitable approach to investigate the heterogeneous function and phenotype of CAFs PMID: 28364361 these findings support that PIKE amplification or overexpression coordinately acts with CDK4 to drive glioblastoma tumorigenesis. PMID: 28368413 Specific E2Fs also have prognostic value in breast cancer, independent of clinical parameters. We discuss here recent advances in understanding of the RB-E2F pathway in breast cancer. We also discuss the application of genome-wide genetic screening efforts to gain insight into synthetic lethal interactions of CDK4/6 inhibitors in breast cancer for the development of more effective combination therapies. PMID: 26923330 p16 in combination with MDM2 and CDK4 immunohistochemistry may help in the differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma. PMID: 27597521 conclude that p16 is highly sensitive for retroperitoneal DDL. However, the lack of specificity limits the diagnostic utility compared with the more established markers MDM2 and CDK4 PMID: 26509911 CDK4 overexpression is associated with cancer. PMID: 27206849 High CDK4 expression is associated with Melanoma. PMID: 26988987 Staining for MDM2 and CDK4 was noted in 25/56 and 23/56 atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), respectively, giving a sensitivity of 45% and 41% and a specificity of 98% and 92%. Staining was noted exclusively in the nuclei of atypical cells and not in the nuclei of adipocytes. Staining for MDM2 and CDK4 occurred in 2/125 and 10/117 benign lipomatous lesions, respectively. PMID: 27508976 Cdk4 inhibition leads to directing human mesenchymal stem cells to a multipotent neurogenic fate by inactivating Smads-STAT3 signaling. PMID: 27192561 Reduced SIRT2 expression during tumorigenesis failed to repress cyclindependent kinase 4 expression, which eventually led to accelerated cell proliferation. PMID: 28259910 older patients with head and neck squamous cell carcinoma and lung cancer have raised serums CDK4 levels, which has the potential to emerge as a biomarker in clinical practice PMID: 27815686 we illustrate that the miR-124/CDK4 axis plays an important role in radiation sensitivity of human esophageal cancer cells by targeting CDK4. PMID: 27323123 MiR-16 upregulation could reduce CDK4 expression. PMID: 26383521 both miR-613 mimics and inhibitors could decrease and increase CDK4 protein levels in non-small cell lung cancer-derived cells, respectively. PMID: 26744345 Upregulation of CDK4 expression is associated with gastric cancer. PMID: 26735582 Our studies demonstrate that CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma . PMID: 26993269 miR-539 plays an important role in the initiation and progression of nasopharyngeal carcinoma by targeting CDK4. PMID: 26559153 The concept that cotargeting MEK and CDK4/6 would prove efficacious in KRAS-mutant (KRAS(mt)) colorectal cancers. PMID: 26369631 This review highlights our current understanding of CDK signaling in both normal and malignant breast tissues, with special attention placed on recent clinical advances in inhibition of CDK4/6 in ER+ disease PMID: 26857361 concurrent inhibition of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased progression-free survival in advanced patients PMID: 25991817 amplification of HMGA2 was associated with the atypical lipomatous tumor/well-differentiated liposarcoma histological type and a good prognosis, whereas CDK4 and JUN amplifications were associated with dedifferentiated liposarcoma histology PMID: 26336885 CDK4 Amplification Reduces Sensitivity to CDK4/6 Inhibition in Fusion-Positive Rhabdomyosarcoma PMID: 25810375 Observations disclose the presence of CDK4 protein in human erythrocytes and its involvement in suicidal erythrocyte death. PMID: 26418250 Data show that the p16/CDKN2A-cyclin-dependent kinase 4 (CDK4)-RB1 protein pathway is frequently disrupted in fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP). PMID: 25852058

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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