Product: p21 Cip1 Antibody
Catalog: DF6423
Description: Rabbit polyclonal antibody to p21 Cip1
Application: WB IHC IF/ICC
Reactivity: Human, Mouse, Rat
Prediction: Horse, Rabbit, Dog
Mol.Wt.: 21kDa; 18kD(Calculated).
Uniprot: P38936
RRID: AB_2838386

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 100ul $280 In stock
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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Horse(83%), Rabbit(100%), Dog(83%)
Clonality:
Polyclonal
Specificity:
p21 Cip1 Antibody detects endogenous levels of total p21 Cip1.
RRID:
AB_2838386
Cite Format: Affinity Biosciences Cat# DF6423, RRID:AB_2838386.
Conjugate:
Unconjugated.
Purification:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

CAP20; CDK-interacting protein 1; CDKI; CDKN1; Cdkn1a; CDN1A_HUMAN; CIP1; Cyclin Dependent Kinase Inhibitor 1A; Cyclin-dependent kinase inhibitor 1; Cyclin-dependent kinase inhibitor 1A (P21); Cyclin-dependent kinase inhibitor 1A (p21, Cip1); DNA Synthesis Inhibitor; MDA-6; MDA6; Melanoma differentiation-associated protein 6; Melanoma differentiation-associated protein; p21; P21 protein; p21CIP1; p21Cip1/Waf1; p21WAF; PIC1; SDI1; SLC12A9; WAF1; Wild type p53 activated fragment 1 (WAF1); Wild type p53 activated fragment 1; Wildtype p53-activated fragment 1;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
P38936 CDN1A_HUMAN:

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

Description:
The tumor suppressor protein p21 Waf1/Cip1 acts as an inhibitor of cell cycle progression. It functions in stoichiometric relationships forming heterotrimeric complexes with cyclins and cyclin-dependent kinases. In association with CDK2 complexes, it serves to inhibit kinase activity and block progression through G1/S (1). However, p21 may also enhance assembly and activity in complexes of CDK4 or CDK6 and cyclin D (2). The carboxy-terminal region of p21 is sufficient to bind and inhibit PCNA, a subunit of DNA polymerase, and may coordinate DNA replication with cell cycle progression (3). Upon UV damage or during cell cycle stages when cdc2/cyclin B or CDK2/cyclin A is active, p53 is phosphorylated and upregulates p21 transcription via a p53-responsive element (4). Protein levels of p21 are downregulated through ubiquitination and proteasomal degradation (5).
Sequence:
MSEPAGDVRQNPCGSKACRRLFGPVDSEQLSRDCDALMAGCIQEARERWNFDFVTETPLEGDFAWERVRGLGLPKLYLPTGPRRGRDELGGGRRPGTSPALLQGTAEEDHVDLSLSCTLVPRSGEQAEGSPGGPGDSQGRKRRQTSMTDFYHSKRRLIFSKRKP

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Rabbit
100
Horse
83
Dog
83
Pig
0
Bovine
0
Sheep
0
Xenopus
0
Zebrafish
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P38936 As Substrate

Site PTM Type Enzyme
S2 Acetylation
S15 Phosphorylation
K16 Ubiquitination
S31 Phosphorylation
T57 Phosphorylation Q16539 (MAPK14) , P28482 (MAPK1) , P45983 (MAPK8) , P49841 (GSK3B)
K75 Ubiquitination
T80 Phosphorylation
S98 Phosphorylation Q99683 (MAP3K5) , P45983 (MAPK8)
S114 Phosphorylation P49841 (GSK3B)
S116 Phosphorylation
S123 Phosphorylation
S130 Phosphorylation Q16539 (MAPK14) , P45983 (MAPK8) , P24941 (CDK2) , P28482 (MAPK1) , Q00534 (CDK6)
K141 Acetylation
K141 Ubiquitination
T145 Phosphorylation P31749 (AKT1) , Q9P1W9 (PIM2) , O14757 (CHEK1) , O43293 (DAPK3) , P11309 (PIM1)
S146 Phosphorylation P53355 (DAPK1) , O14757 (CHEK1) , P11309 (PIM1) , Q9NRM7 (LATS2) , Q9P1W9 (PIM2) , P17252 (PRKCA) , Q05655 (PRKCD) , P31749 (AKT1) , Q15208 (STK38)
Y151 Phosphorylation
S153 Phosphorylation P17252 (PRKCA) , Q9Y463 (DYRK1B)
K154 Acetylation
K154 Ubiquitination
R156 Methylation
S160 Phosphorylation
K161 Acetylation
K161 Ubiquitination
K163 Acetylation
K163 Ubiquitination

Research Backgrounds

Function:

May be involved in p53/TP53 mediated inhibition 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. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding. Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest.

PTMs:

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. UV radiation-induced phosphorylation at Thr-80 by LKB1 and at Ser-146 by NUAK1 leads to its degradation.

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. Ubiquitination at Ser-2 leads to degradation by the proteasome pathway. Ubiquitinated by RNF114; leading to proteasomal degradation.

Acetylation 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).

Subcellular Location:

Cytoplasm. Nucleus.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

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

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. Interacts with STK11 and NUAK1. Interacts wih DTL. Interacts with isoform 1 and isoform 2 of TRIM39.

Family&Domains:

The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment 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.

The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex.

Belongs to the CDI family.

Research Fields

· Cellular Processes > Cell growth and death > Cell cycle.   (View pathway)

· Cellular Processes > Cell growth and death > p53 signaling pathway.   (View pathway)

· Cellular Processes > Cell growth and death > Cellular senescence.   (View pathway)

· Environmental Information Processing > Signal transduction > ErbB signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > HIF-1 signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > FoxO signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > PI3K-Akt signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Jak-STAT signaling pathway.   (View pathway)

· Human Diseases > Drug resistance: Antineoplastic > Endocrine resistance.

· Human Diseases > Drug resistance: Antineoplastic > Platinum drug resistance.

· Human Diseases > Infectious diseases: Viral > Hepatitis C.

· Human Diseases > Infectious diseases: Viral > Hepatitis B.

· Human Diseases > Infectious diseases: Viral > Human papillomavirus infection.

· Human Diseases > Infectious diseases: Viral > HTLV-I infection.

· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Overview > Transcriptional misregulation in cancer.

· Human Diseases > Cancers: Overview > Viral carcinogenesis.

· Human Diseases > Cancers: Overview > Proteoglycans in cancer.

· Human Diseases > Cancers: Overview > MicroRNAs in cancer.

· Human Diseases > Cancers: Specific types > Colorectal cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Renal cell carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Pancreatic cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Endometrial cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Glioma.   (View pathway)

· Human Diseases > Cancers: Specific types > Prostate cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Thyroid cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Basal cell carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Melanoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Bladder cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Chronic myeloid leukemia.   (View pathway)

· Human Diseases > Cancers: Specific types > Small cell lung cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Non-small cell lung cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Breast cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

· Organismal Systems > Endocrine system > Oxytocin signaling pathway.

References

1). Crocetin inhibits the proliferation, migration and TGF-β 2-induced epithelial-mesenchymal transition of retinal pigment epithelial cells . European Journal of Pharmacology, 2017 (PubMed: 28970011) [IF=5.0]

Application: WB    Species: human    Sample:

Figure 2. Crocetin induces cell cycle arrest and influences PCNA, p21, and p53 expression in RPE cells. (A) Cells were harvested after treatment with or without 50 and 100 μM crocetin for 24 h. DNA was stained with PI for flow cytometric analysis. The number of cells in G1 phase was significantly increased in the crocetin-treated group compared with that in the untreated group. (B) Cells were treated or without with 50, 100 and 200 μM crocetin for 48 h. Western blot analysis was used to evaluated the expression of PCNA, p21, p53 and the housekeeping protein β-actin. *P< 0.05 vs 0 μM crocetin, **P< 0.01 vs 0 μM crocetin. The data are presented as the mean ± S.D. (n = 3/group).

2). Impact of a high‑fat diet on intestinal stem cells and epithelial barrier function in middle‑aged female mice. Molecular Medicine Reports, 2020 (PubMed: 32016468) [IF=3.4]

Application: IHC    Species: Mice    Sample: apoptotic cells

Figure 6. Cell apoptosis in the small intestine was not affected by HFD. (A) Ileal sections stained for apoptotic cells (scale bar, 100 µm; magnification, ×20). Quantification of apoptotic cells among (B) villi and (C) crypt sections. (D) Expression of P21 in the small intestine, examined using immunohistochemistry (scale bars, 100 µm; magnification, ×40). Quantification of P21 positive cells as a percentage of the (E) crypts and (F) villi. (G) Immunohistochemical assay for P53 in the small intestine (scale bars, 100 µm; magnification, ×40). Quantification of P53 positive cells as a percentage of the (H) crypts and (I) villi. (J) P21 and (K) P53 mRNA expression levels in the small intestine. Data are presented as the mean ± standard deviation. HFD, high-fat diet; Con, control.

3). TRIM50 Inhibits Proliferation and Metastasis of Gastric Cancer via Promoting β-Catenin Degradation. Journal of Oncology, 2022 (PubMed: 36046365)

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