p21CIP1 recombinant protein

p21CIP1 recombinant protein

Cat. Num. AAA515251

• Gene Names: CDKN1A; P21; CIP1; SDI1; WAF1; CAP20; CDKN1; MDA-6; p21CIP1
• Applications: Western Blot
• Purity: >70%
• Synonyms: p21CIP1; p21CIP1 recombinant protein; CDKN1A; P21; SDI1; WAF1; CAP20; CDKN1; MDA-6

• Purity/Purification: >70%
• Form/Format: 50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol.
• Concentration: 0.2 ug/ul (varies by lot)
• Sequence Length: 2175

• Applicable Applications for p21CIP1 recombinant protein: Kinase Assay, Western Blot (WB)
• Scientific Background: CIP 1 (Cyclin-Dependent Kinase Inhibitor 1A) regulates cell cycle progression, terminal differentiation, and apoptosis (1). CIP1 was shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinase (CDK) activity. DNA damage leads to increased expression of CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells (2).
• Expression System: E.coli
• Species: Human
• Preparation and Storage: Store product at -70°C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.; Shipping: Ships with dry ice

SDS-PAGE

(The purity was determined to be >70% by densitometryApprox. MW 46kDa)

Related Product Information for p21CIP1 recombinant protein

Recombinant full-length human p21CIP1 was expressed in E. coli cells using a N-terminal GST tag.

Scientific Background: CIP 1 (Cyclin-Dependent Kinase Inhibitor 1A) regulates cell cycle progression, terminal differentiation, and apoptosis (1). CIP1 was shown to be induced by p53 and to be a potent inhibitor of cyclin-dependent kinase (CDK) activity. DNA damage leads to increased expression of CIP1 in cyclin E-containing complexes and to an associated decrease in cyclin-dependent kinase activity. CIP1 is a critical downstream effector in the p53-specific pathway of growth control in mammalian cells (2).

Product Categories/Family for p21CIP1 recombinant protein

Cell Cycle Proteins; Signaling Proteins - Cell Cycle Proteins

References

1. el-Deiry, W S. et al: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 1994;54(5):1169-74
2. Wagner, M. et al: Cyclin-dependent kinase-inhibitor 1 (CDKN1A) in the squamous epithelium of the oropharynx: possible implications of molecular biology and compartmentation. Anticancer Res. 2001; 21(1A):333-45.

NCBI and Uniprot Product Information

• NCBI GI #: 310832422
• NCBI GeneID: 1026
• NCBI Accession #: NP_000380.1
• NCBI GenBank Nucleotide #: NM_000389
• UniProt Accession #: P38936; Q14010; Q9BUT4
• Molecular Weight: ~46 kDa
• NCBI Official Full Name: Homo sapiens cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A), transcript variant 1, mRNA
• NCBI Official Synonym Full Names: cyclin-dependent kinase inhibitor 1A (p21, Cip1)
• NCBI Official Symbol: CDKN1A
• NCBI Official Synonym Symbols: P21; CIP1; SDI1; WAF1; CAP20; CDKN1; MDA-6; p21CIP1
• NCBI Protein Information: cyclin-dependent kinase inhibitor 1; DNA synthesis inhibitor; CDK-interacting protein 1; CDK-interaction protein 1; wild-type p53-activated fragment 1; melanoma differentiation associated protein 6
• UniProt Protein Name: Cyclin-dependent kinase inhibitor 1
• UniProt Gene Name: CDKN1A
• UniProt Synonym Gene Names: CAP20; CDKN1; CIP1; MDA6; PIC1; SDI1; WAF1; MDA-6
• UniProt Entry Name: CDN1A_HUMAN

NCBI Description

This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Nov 2010]

Uniprot Description

Function: May be the important intermediate by which p53/TP53 mediates its role as an inhibitor of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Ref.1 Ref.13

Subunit structure: Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21

By similarity. Interacts with MKRN1. Interacts with PSMA3. Interacts with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Interacts with PIM1. Ref.13 Ref.14 Ref.16 Ref.19 Ref.21 Ref.23 Ref.24

Subcellular location: Cytoplasm. Nucleus Ref.13 Ref.15 Ref.16.

Tissue specificity: Expressed in all adult tissues, with 5-fold lower levels observed in the brain.

Induction: Activated by p53/TP53, mezerein (antileukemic compound) and IFNB1. Repressed by HDAC1. Ref.1 Ref.2

Domain: The PIP-box K+4 motif mediates both the interaction with PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination. Ref.19 Ref.21The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex. Ref.19 Ref.21

Post-translational modification: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by PIM2 enhances CDKN1A stability and inhibits cell proliferation. Phosphorylation of Thr-145 by PIM1 results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability.Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Ref.19 Ref.20 Ref.21 Ref.24 Ref.25Acetylation leads to protein stability. Acetylated in vitro on Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1

By similarity.

Sequence similarities: Belongs to the CDI family.

Sequence caution: The sequence AAB59559.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.The sequence AAB59560.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.