3 exons (68, 450, 1600 pb ; the first exon is not translated)

2,1 kb mRNA, expression regulated at both transcriptional and post-transcriptional levels.

164 amino acids, 18 kDa. Contains interacting domains with several proteins (see Figure) and a nuclear localization signal.

in all adult human tissues. CDKN1A expression in the developing mouse embryo is correlated with cell-cycle arrest that precedes terminal differentiation in a variety of tissues.

nuclear and cytoplasmic.

located predominantly in the nucleus.

relocalization to the cytoplasm during the differentiation of immature monocytes.

can interact with cytoplasmic proteins ( pro-caspase-3, ASK-1, JNK, CaM, cyclinD-CDK4).

CDKN1A is implicated in regulation of cell growth and cell response to DNA damage. It inhibits cell cycle progression in G1 by binding to G1 cyclin-CDK complexes and to PCNA antigen and may also induce G2 arrest. In response to DNA damage p53 induces CDKN1A expression, which is responsible for the cell cycle arrest at the G1 checkpoint. CDKN1A plays also a role in the protection of cells against apoptosis and its expression is essential to maintain cell survival during differentiation of several cell lineages.

with p27kip1 and p57kip2 in the N- terminal.

Analysis of normal and tumor cells revealed two common variants in the CDKN1A gene which were not unique to tumors: a C to A substitution at codon 31 (Ser 31-to-Arg) which does not result in loss of activity and a C to T change in the 3 untranslated region of the CDKN1A gene, 20 bp following the stop codon. In prostate cancer, a single base insertion at codon 35, resulting in frameshift, protein troncation and impairement of activity, has been identified. A Phe to Leu change at codon 63, an Arg to Trp change at position 94 and an Asn to Ser change at position 50 were observed in a Burkitts lymphoma, a human breast carcinoma and a malignant melanoma cell line, respectively.