CDKN1A

GeneName

CDKN1A

Summary

CDKN1A, also known as p21, Cip1, or WAF1, is an 18 kDa cyclin-dependent kinase inhibitor that plays a pivotal role in regulating the cell cycle, particularly the G1/S transition. It is expressed in various tissues and localised in the nucleus, cytoplasm, and nucleolus. CDKN1A functions by binding to and inhibiting cyclin-CDK complexes, thereby preventing the phosphorylation of target proteins necessary for cell cycle progression. It is also involved in cellular responses to stress, such as DNA damage and UV radiation, and participates in processes like cellular senescence and apoptosis, often acting in conjunction with the tumour suppressor protein p53. Additionally, CDKN1A is known to form complexes with proliferating cell nuclear antigen (PCNA) and plays a role in DNA repair and replication.

Importance

CDKN1A is relevant to: - Cancer research due to its role in cell cycle regulation and its association with tumour suppression. - Studies on cellular senescence and aging, as it mediates responses to stress and DNA damage. - Regenerative medicine, given its involvement in tissue regeneration and wound healing processes. - Understanding mechanisms of heart development and repair, as it negatively regulates cardiac muscle tissue regeneration. - Research on immune responses, particularly in relation to B cell proliferation and differentiation.

Top Products

For researchers investigating CDKN1A, we highly recommend the top-selling recombinant antibody, Anti-p21 antibody [EPR362] (ab109520). This antibody has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry (FC), and immunoprecipitation (IP). With 537 citations, it is well-regarded in the research community, demonstrating its reliability and effectiveness for CDKN1A detection. This makes it an excellent choice for those seeking consistent and robust results in their studies. "The Human p21 ELISA Kit (ab214658), with 3 citations, is an excellent option for researchers looking to measure CDKN1A levels in their samples."

Abcam Product Citation Summary

The data indicates that CDKN1A is frequently studied in the context of cellular senescence across various species, particularly in human and mouse models. The use of Abcam antibodies in Western blotting highlights its role in diverse biological processes, including apoptosis, cell cycle regulation, and responses to treatments in different cell types, such as stem cells, cancer cells, and progenitor cells. The studies span a range of conditions, including Marfan syndrome, liver cancer, and cardiac function, suggesting the importance of CDKN1A in both normal physiology and disease states.

Abcam Product Citation Table

Domain

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.

Function

Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). 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 (PubMed:11595739). Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity).

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. 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).

Sequence Similarities

Belongs to the CDI family.

Tissue Specificity

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

Cellular localization

• Cytoplasm
• Nucleus

Alternative names

CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1, CDKN1A, Cyclin-dependent kinase inhibitor 1, CDK-interacting protein 1, Melanoma differentiation-associated protein 6, p21, MDA-6

Database links

swissprot:P38936 entrezGene:1026 omim:116899

Other research areas

• Epigenetics
• Immuno-oncology