产品: p21 Cip1 抗体
货号: AF6290
描述: Rabbit polyclonal antibody to p21 Cip1
应用: WB IF/ICC
反应: Human, Mouse, Rat
预测: Bovine, Horse, Sheep, Rabbit, Dog
分子量: 21kDa; 18kD(Calculated).
蛋白号: P38936
RRID: AB_2827699

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产品描述

来源:
Rabbit
应用:
WB 1:500-1:2000, IF/ICC 1:100-1:500
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Mouse,Rat
预测:
Bovine(100%), Horse(91%), Sheep(100%), Rabbit(83%), Dog(100%)
克隆:
Polyclonal
特异性:
p21 Cip1 Antibody detects endogenous levels of total p21 Cip1.
RRID:
AB_2827699
引用格式: Affinity Biosciences Cat# AF6290, RRID:AB_2827699.
偶联:
Unconjugated.
纯化:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
保存:
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.
别名:

展开/折叠

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;

抗原和靶标

免疫原:
Uniprot:
基因/基因ID:
表达:
P38936 CDN1A_HUMAN:

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

描述:
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.
序列:
MSEPAGDVRQNPCGSKACRRLFGPVDSEQLSRDCDALMAGCIQEARERWNFDFVTETPLEGDFAWERVRGLGLPKLYLPTGPRRGRDELGGGRRPGTSPALLQGTAEEDHVDLSLSCTLVPRSGEQAEGSPGGPGDSQGRKRRQTSMTDFYHSKRRLIFSKRKP

种属预测

种属预测:

score>80的预测可信度较高,可尝试用于WB检测。*预测模型主要基于免疫原序列比对,结果仅作参考,不作为质保凭据。

Species
Results
Score
Bovine
100
Sheep
100
Dog
100
Horse
91
Rabbit
83
Zebrafish
67
Xenopus
56
Pig
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

翻译修饰 - P38936 作为底物

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

研究背景

功能:

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.

翻译修饰:

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).

细胞定位:

Cytoplasm. Nucleus.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
组织特异性:

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

亚基结构:

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.

蛋白家族:

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.

研究领域

· 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.

文献引用

1). Sirt3-mediated mitophagy regulates AGEs-induced BMSCs senescence and senile osteoporosis. Redox Biology (PubMed: 33662874) [IF=11.4]

Application: WB    Species: mice    Sample: bone marrow mesenchymal stem (BMSCs)

Fig. 1. Effects of AGEs in different concentrations on the senescence of BMSCs. The BMSCs were treated with AGEs (50–200 μg/mL) or BSA for 24–72 h. (A) SA-β-gal assay for detection of BMSCs senescence. Scale bar: 100 μm. (B) Detection of H3K9me3 by immunofluorescence in BMSCs. Scale bar: 100 μm. (C) Detection of γ-H2AX by immunofluorescence in BMSCs. Scale bar: 100 μm. (D–I) Representative Western blotting assay and quantitation of the level of P16, P21, P53. **p < 0.01 versus BSA.

2). KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner. Cell Death & Disease (PubMed: 37156774) [IF=9.0]

Application: WB    Species: Human    Sample: MCF7 cells

Fig. 4 KLF12 reduces the stability of p53. a Western blot assay showed changes of exogenous p53 in HEK293T cells transfected with increasing doses of KLF12. b Changes in endogenous p53 and p21 in MCF7 cells transfected with increasing doses of KLF12 by Western blot assay. c Changes in the endogenous level of p53 and p21 in ZR-75-30 cells transfected with NC, shKLF12#1, or shKLF12#2 by Western blot assay. d Changes in exogenous p53 in HEK293T cells transfected with GFP-KLF12 without and with 20 μg/ml MG132 treatment by Western blot assay. e, f The half-life of p53 in MCF-7 cells with overexpressed KLF12 treated with CHX (50 μg/ml) by Western blot assay. g CoIP assay showed changes in the level of ubiquitinated p53 in HEK293T cells transfected with Flag-KLF12 plus 4 h treatment with 20 μg/ml MG132. h CoIP assay detected changes in K48-linked polyubiquitylation of p53 and K63-linked polyubiquitylation of p53 in HEK293T cells. The cells were treated with MG132 for 4 h following transfection.

3). Histone acetylation plays an important role in MC-LR-induced apoptosis and cycle disorder in SD rat testicular cells. Chemosphere (PubMed: 31683423) [IF=8.8]

Application: WB    Species: Rat    Sample: testicular tissue

Fig4. The effect of TSA and MC-LR on cell cycle-related genes and proteins 434 levels in co-cultured Sertoli-germ cells and SD rat testicular tissues. (A) 435 Expressions of cell cycle-related genes in vitro and (B) expressions of cell 436 cycle-related genes in vivo were detected by RT-qPCR. (C) Expressions of cell cycle-related proteins in vitro and (D) expressions of cell cycle-related proteins in 438 vivo were detected by western blotting. (E) Quantitative analysis of proteins 439 expression levels in vitro. (F) Quantitative analysis of proteins expression levels in 440 vivo. (*P<0.05 vs. the control group; #P<0.05 vs. the 36 µM MC-LR group or the 40 441 µg kg-1 MC-LR group)

4). d-Borneol enhances cisplatin sensitivity via p21/p27-mediated S-phase arrest and cell apoptosis in non-small cell lung cancer cells and a murine xenograft model. Cellular & Molecular Biology Letters (PubMed: 35883026) [IF=8.3]

5). Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation. Phytomedicine (PubMed: 37301185) [IF=7.9]

6). VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis. Free Radical Biology and Medicine (PubMed: 36402439) [IF=7.4]

7). Integrating scRNA and bulk-RNA sequencing develops a cell senescence signature for analyzing tumor heterogeneity in clear cell renal cell carcinoma. Frontiers in Immunology (PubMed: 37503331) [IF=7.3]

Application: WB    Species: Human    Sample: 786-O cell

Figure 8 Construction of risk model and functional validation of critical genes. (A) Differential analysis between clust1 and no_clust1 in TCGA dataset; (B) Differential analysis between clust2 and no_clust2 in TCGA dataset; (C) Differential analysis between clust3 and no_clust3 in TCGA dataset; (D) A total of 961 promising candidates were identified among the differentially expressed genes; (E) Trajectory of each independent variable as lambda changes; (F) Confidence interval under lambda; (G) Coefficients of prognostic-related genes obtained from multivariate Cox analysis; (H) Western blot assay of DUSP1 protein expression in 786-O cell after transfection of Si-DUSP1; (I) Colony formation assay was carried out to evaluate the proliferation of 786-O cell; (J, K) Transwell assay was used to assess the migration and invasion of 786-O cell. (L) Western blot assay of p21 and p53 protein expression in 786-O cell after transfection of Si-DUSP1. *, p< 0.05; (M) SA-β-gal staining of 786-O cell. *, p< 0.05.

8). Primary microcephaly gene CENPE is a novel biomarker and potential therapeutic target for non-WNT/non-SHH medulloblastoma. Frontiers in Immunology (PubMed: 37593739) [IF=7.3]

Application: WB    Species: Human    Sample:

Figure 9 CENPE regulates the cell cycle and p53 pathway of non-WNT/non-SHH MB. (A–E) Western blot showed that the protein level of CENPE, P53, P21 and CDK1 by the knockdown of CENPE (mean ± SD, n = 3). (F–H) Flow cytometry was used to detect the cell cycle (mean ± SD, n = 3).

9). Neuroprotective effects of salidroside on ageing hippocampal neurons and naturally ageing mice via the PI3K/Akt/TERT pathway. PHYTOTHERAPY RESEARCH (PubMed: 34374127) [IF=7.2]

10). Mechanical stretching can modify the papillary dermis pattern and papillary fibroblast characteristics during skin regeneration. Journal of Investigative Dermatology (PubMed: 35181299) [IF=6.5]

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