We have created two knock-in mouse models to study the mechanisms that regulate p27 in normal cells and cause misregulation of p27 in tumors: p27(S10A), in which Ser10 is mutated to Ala; and p27(CK-), in which point mutations abrogate the ability of p27 to bind cyclins and CDKs. These two mutant alleles identify steps in a pathway that controls the proteasomal degradation of p27 uniquely in qui...

يا هچروم يدنب هشوخ متيروگلا ياراد پ ا ار يددعتم ياهرتم هلمج زا ،نتشادرب هب طوبرم ياهرتماراپ نتشاذگ اه هداد ديد عاعش ، يم هك دشاب ريثات و دنراد متيروگلا ييارگمه و دركلمع رد يدايز اطخ و شيامزآ تروص هب لاومعم نييعت يم رگ د دن . شور هلاقم نيا رد ي رب ينتبم CLA-PSO 1 ي هتسسگ لدم كي هك PSO دشاب يم يارب قيبطت كيتاموتا پ ياهرتمارا يا هچروم يدنب هشوخ يم داهنشيپ ددرگ . روظنم هب گلا ساسا رب هك د...

The high-dimensional search space involved in markerless full-body articulated human motion tracking from multiple-views video sequences has led to a number of solutions based on metaheuristics, the most recent form of which is Particle Swarm Optimization (PSO). However, the classical PSO suffers from premature convergence and it is trapped easily into local optima, significantly affecting the ...

The p27(Kip1) protein associates with G1-specific cyclin-CDK complexes and inhibits their catalytic activity. p27(Kip1) is regulated at various levels, including translation, degradation by the ubiquitin/proteasome pathway and non-covalent sequestration. Here, we describe point mutants of p27 deficient in their interaction with either cyclins (p27(c-)), CDKs (p27(k-)) or both (p27(ck-)), and de...

The majority of thyroid carcinomas maintain the expression of the cell growth suppressor p27, an inhibitor of cyclin-dependent kinase-2 (Cdk2). However, we find that 80% of p27-expressing tumors show an uncommon cytoplasmic localization of p27 protein, associated with high Cdk2 activity. To reproduce such a situation, a mutant p27 devoid of its COOH-terminal nuclear-localization signal was gene...

The cyclin-dependent kinase inhibitor p27(Kip1) is degraded in late G(1) phase by the ubiquitin-proteasome pathway, allowing cells to enter S phase. Due to accelerated degradation of p27(Kip1), various human cancers express low levels of p27(Kip1) associated with poor prognosis. S-phase kinase-associated protein 2, the F-box protein component of an SCF ubiquitin ligase complex, is implicated in...

The cellular abundance of the cyclin-dependent kinase (Cdk) inhibitor p27 is regulated by the ubiquitin-proteasome system. Activation of p27 degradation is seen in proliferating cells and in many types of aggressive human carcinomas. p27 can be phosphorylated on threonine 187 by Cdks, and cyclin E/Cdk2 overexpression can stimulate the degradation of wild-type p27, but not of a threonine 187-to-...

We investigated the effects of melatonin, cetuximab and cisplatin treatments alone or in combination on PANC-1 cells from a human pancreatic carcinoma ductal cell origin through viability gene expressions. The were left for 48 h incubation after applying chemicals cells. metabolic substances at end measured by MTT assay. expressions p21, p27, p53, p57, MDM2 KRAS determined RT-PCR. use melatonin...

The p27 cyclin-dependent kinase inhibitor is a negative regulator of cell-cycle progression. In many human epithelial malignancies, decreased expression of p27 correlates with high grade, early recurrence, and poor prognosis. To evaluate the prognostic significance of p27 in hepatocellular carcinoma (HCC), we studied 54 HCCs along with corresponding nontumoral tissue. Immunohistochemistry (IHC)...