CDK3 Human

Cyclin-Dependent Kinase 3 Human Recombinant
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Description

Functional Roles in Cell Cycle Regulation

CDK3 operates at two critical checkpoints:

  1. G0-G1 Transition:

    • Forms complexes with cyclin C to phosphorylate RB1, enabling E2F-mediated transcription of S-phase genes .

    • Peaks in mid-G1 phase, distinct from CDK2/4/6 activity patterns .

  2. G1-S Progression:

    • Phosphorylates histone H1 and transcriptional activators (e.g., c-JUN, ATF1) to promote DNA synthesis .

    • Dominant-negative CDK3 mutants induce G1 arrest, unrecoverable by CDK2 .

Overexpression in Tumorigenesis

  • Nasopharyngeal Carcinoma (NPC):

    • 3.5-fold higher protein levels in NPC cell lines (CNE1, CNE2) vs. normal nasopharyngeal epithelium .

    • Correlates with advanced T/N classification and clinical stage (p<0.05) .

  • Glioblastoma:

    • Elevated CDK3 enhances ATF1/NFAT3 phosphorylation, driving cell transformation .

    • siRNA-mediated CDK3 knockdown reduces soft-agar colony formation by 60% .

Biomarker Potential

  • Immune Microenvironment Modulation:

    • CDK3 inversely correlates with cytotoxic CD8+ T-cell infiltration (r=−0.238; p=1.24e-06) in CRC, suggesting immunosuppressive effects .

  • Therapeutic Strategies:

    • CDK3 Inhibitors: Preclinical agents targeting CDK3-cyclin complexes show efficacy in RAS-driven tumors .

    • Combination Therapy: Synergy observed with EGFR/RAS pathway inhibitors in in vitro models .

Research Gaps and Future Directions

  • Mechanistic Ambiguities: The dual role of CDK3 as oncogene (in glioblastoma/NPC) vs. tumor suppressor (in CRC) remains unresolved.

  • Technical Limitations: Most studies rely on bulk RNA sequencing; single-cell analyses are needed to address tumor heterogeneity .

  • Clinical Trials: No phase III trials targeting CDK3 exist, though early-phase studies are underway for CDK3/ATF1 axis inhibitors .

Product Specs

Introduction
Cyclin-dependent kinase 3, also known as CDK3, is a member of the cyclin-dependent protein kinase family. It plays a role in promoting entry into the S phase of the cell cycle, partly by activating E2F family transcription factors. CDK3 associates with cyclin C and phosphorylates the retinoblastoma one protein to facilitate exit from the G0 phase.
Description
Recombinant human CDK3, produced in E. coli, is a single polypeptide chain consisting of 328 amino acids (residues 1-305) with a molecular weight of 37.4 kDa. It includes a 23 amino acid His-tag fused at the N-terminus and is purified using proprietary chromatographic techniques.
Physical Appearance
A sterile, colorless solution that has been filtered.
Formulation
The CDK3 solution has a concentration of 0.25 mg/ml and is supplied in a buffer containing 20 mM Tris-HCl (pH 8.0), 1 M urea, and 10% glycerol.
Stability
For short-term storage (up to 2-4 weeks), keep at 4°C. For extended storage, freeze at -20°C. Adding a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Avoid repeated freeze-thaw cycles.
Purity
Purity is determined to be greater than 85% by SDS-PAGE analysis.
Synonyms
Cyclin-dependent kinase 3, Cell division protein kinase 3, CDK3, CDKN3.
Source
Escherichia Coli.
Amino Acid Sequence
MGSSHHHHHH SSGLVPRGSH MGSMDMFQKV EKIGEGTYGV VYKAKNRETG QLVALKKIRL DLEMEGVPST AIREISLLKE LKHPNIVRLL DVVHNERKLY LVFEFLSQDL KKYMDSTPGS ELPLHLIKSY LFQLLQGVSF CHSHRVIHRD LKPQNLLINE LGAIKLADFG LARAFGVPLR TYTHEVVTLW YRAPEILLGS KFYTTAVDIW SIGCIFAEMV TRKALFPGDS EIDQLFRIFR MLGTPSEDTW PGVTQLPDYK GSFPKWTRKG LEEIVPNLEP EGRDLLMQLL QYDPSQRITA KTALAHPYFS SPEPSPAARQ YVLQRFRH.

Product Science Overview

Introduction

Cyclin-Dependent Kinase 3 (CDK3) is a serine/threonine-protein kinase that plays a critical role in the regulation of the eukaryotic cell cycle. It is involved in the transitions between the G0-G1 and G1-S phases of the cell cycle . CDK3 is part of the larger family of cyclin-dependent kinases (CDKs), which are characterized by their dependency on a regulatory subunit known as a cyclin .

Gene and Protein Structure

The CDK3 gene is located on chromosome 17 at the band 17q25.1 in humans . The protein encoded by this gene is known as Cyclin-Dependent Kinase 3 or Cell Division Protein Kinase 3. CDK3 has several aliases, including CDK3 and cyclin-dependent kinase 3 . The protein structure of CDK3 includes domains essential for its enzymatic activity, which are provided by its interaction with cyclins .

Function and Mechanism

CDK3 is involved in the regulation of the cell cycle by phosphorylating specific substrates, such as histone H1 . It interacts with cyclin-C (CCNC) during the interphase of the cell cycle . This interaction is crucial for the progression of cells from the G0 phase (a resting phase) to the G1 phase (the first gap phase) and subsequently from the G1 phase to the S phase (the synthesis phase) where DNA replication occurs .

Evolutionary Significance

Cyclin-dependent kinases, including CDK3, have undergone significant evolutionary divergence and specialization. They are part of the CMGC group of kinases, which also includes mitogen-activated protein kinases (MAPKs) and glycogen synthase kinase-3 beta (Gsk3β) . The evolutionary expansion of the CDK family in mammals has led to the division of CDKs into several subfamilies, each with specific functions related to cell cycle regulation and transcription .

Clinical Relevance

Deregulation of CDKs, including CDK3, is a hallmark of several diseases, particularly cancer . The importance of CDKs in cell cycle control makes them potential targets for therapeutic interventions. Drug-targeted inhibition of specific CDKs has shown promising results in clinical trials, highlighting their potential in cancer treatment .

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