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Rabbit Anti-phospho-CDKN1A/p21 (Thr57)/FITC Conjugated antibody
background:
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. Two alternatively spliced variants, which encode an identical protein, have been reported.
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.
Subunit:
Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21. 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.
Subcellular Location:
Cytoplasmic and Nuclear.
Tissue Specificity:
Expressed in spleen, liver and lung. Not detected in kidney, colon, stomach or brain.
Post-translational modifications:
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.
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.
Similarity:
Belongs to the CDI family.
Database links:
Entrez Gene: 1026 Human
Entrez Gene: 12575 Mouse
Entrez Gene: 114851 Rat
Omim: 116899 Human
SwissProt: P38936 Human
SwissProt: P39689 Mouse
Unigene: 370771 Human
Unigene: 195663 Mouse
Unigene: 10089 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
p21蛋白的过度表达与肿瘤的类型、恶性度、分期以及病人的预后密切相关。主要用于胃肠道癌肿、乳腺癌、肺癌等恶性肿瘤的研究。
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