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)

Upstream stimulating factors, USF-1 and -2, are members of the evolutionary conserved basic-Helix-Loop-Helix-Leucine Zipper transcription factor family. The ubiquitously expressed USF-1 and -2 proteins of respectively 43 kDa and 44 kDa interact with high affinity to cognate E-box regulatory elements (CANNTG) which are particularly represented over the genome. The USF transcription factors are key regulatory elements of the transcriptional machinery mediating recruitment of chromatin remodelling enzymes, interacting with co-activators and members of the pre-initiation complex (PIC). Furthermore, transcriptionnal activity and DNA-binding of the USF proteins can be modulated by multiple ways including phosphorylation by distinct kinases (p38, protein kinase A and C, cdk1 and PI3Kinase), homo or heterodimerization formation and DNA modification of the E-box binding motif (methylation, SNP). Taken together, these parameters render very complex the understanding of the USF-dependent gene expression regulation. USF transcription factors have thus been involved as key regulators of a wide number of gene regulation network including stress and immune response, cell cycle and proliferation. This review will thus focus on general aspect of the USF transcription factors and their implications in some regulatory networks.
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PMID:[USF as a key regulatory element of gene expression]. 1638 22

TIS21(/BTG2/PC3) has been shown to work as a pan-cell cycle inhibitor and a negative regulator of cyclin B1/cdk1 and forkhead box M1 (FoxM1). Moreover, loss of TIS21 expression has been suggested as an early event in carcinogenesis of thymus, prostate, kidney, and liver. However, there is no report yet what regulates the in vivo stability of TIS21 protein. Here, TIS21 was found to be a target of ubiquitin ligase, S phase kinase associated protein 2 (Skp2), the expression of which was regulated by FoxM1. Leucine rich repeat (LRR) domain of Skp2 could bind to TIS21 C-terminus and facilitated TIS21 degradation via ubiquitin-proteasome pathway. Skp2 without LRR and C-terminus deleted TIS21 (TIS21DeltaC) failed to interact with each other, and failure of their interaction prolonged half-life of TIS21 protein. Furthermore, in vivo function of TIS21, inhibition of cell growth, was regulated by expressions of Skp2 and FoxM1; It was significantly enhanced by knock down of Skp2 expression in the TIS21 adenovirus infected cells, whereas it was significantly ameliorated by co-expression of FoxM1 with TIS21. These data indicate that TIS21 is a novel target of SCF-Skp2 ubiquitin ligase, which is regulated by expression of FoxM1.
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PMID:Skp2 enhances polyubiquitination and degradation of TIS21/BTG2/PC3, tumor suppressor protein, at the downstream of FoxM1. 1961 63