Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA coding for ik3-2 (designated as ik3-2 from an interactor-2 with cdk3) was cloned by cross-hybridization with ik3-1 and RT-PCR. Analysis of amino acid sequence indicated that ik3-2 has the C-terminal cyclin-box-like region highly homologous to that of ik3-1 (identity in amino acids: 78%). On the other hand, the remainder of ik3-2 gene is not so similar to that of ik3-1. There are several regions other than the C-terminal cyclin-box-like region that are conserved between ik3-1 and ik3-2. In vivo binding assay indicated that like ik3-1, ik3-2 binds to cdk3, cdk5, and c-abl, although ik3-2 binds to cdk3 weakly as compared with ik3-1. The C-terminal cyclin-box-like region of ik3-2 (123 amino acids) is able to be associated with cdk5. Accordingly, ik3-2 is very similar to ik3-1 concerning its molecular interaction with other molecules, suggesting that ik3-2 function in the same biological field as ik3-1. Northern blot analysis indicated that ik3-2 is expressed ubiquitously all over tissues.
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PMID:ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-abl. 1195 25

ik3-2 is a close relative to ik3-1/Cables, an associator with cdk3 and cdk5. ik3-1/Cables has been identified to be a candidate tumor suppressor for colon and head/neck cancers. In agreement, it has been pointed out that ik3-1/Cables is a regulator for both p53- and p73-induced apoptosis [J. Biol. Chem. 277 (2002) 2951] although ectopic expression of ik3-1/Cables does not induce apoptosis. Here we show that adenovirus-mediated overexpression of ik3-2 results in apoptosis of p53-intact U2OS cells. ik3-2 binds to p53 in vivo and ectopic coexpression of ik3-2 enhances apoptosis induced by adenovirus-mediated expression of p53. Furthermore, ectopic expression of ik3-2 results in apoptosis of primary p53/Mdm2- and p53/ARF-null mouse embryo fibroblasts, indicating that ik3-2-induced apoptosis is partially p53-independent. Both the highly conserved C-terminal cyclin box-homologous domain (ik3-2-C) and the N-terminal region consisting of 70 amino acids (ik3-2-N) are responsible for ik3-2-mediated enhancement of p53-induced apoptosis. In contrast, ik3-2-induced p53-independent apoptosis is mediated through ik3-2-N. We thus identified ik3-2 as a proapoptotic factor involved in both p53-mediated and p53-independent apoptotic pathways.
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PMID:ik3-2, a relative to ik3-1/Cables, is involved in both p53-mediated and p53-independent apoptotic pathways. 1463 68