More than 80% of malignant tumors show centrosome amplification and clustering. Centrosome amplification results from aberrations in the centrosome duplication cycle, which is strictly coordinated with DNA-replication-cycle. However, the relationship between cell-cycle regulators and centrosome duplicating factors is not well understood. This report demonstrates that 14-3-3γ localizes to the centrosome and 14-3-3γ loss leads to centrosome amplification. Loss of 14-3-3γ results in the phosphorylation of NPM1 at Thr-199, causing early centriole disjunction and centrosome hyper-duplication. The centrosome amplification led to aneuploidy and increased tumor formation in mice. Importantly, an increase in passage of the 14-3-3γ-knockdown cells led to an increase in the number of cells containing clustered centrosomes leading to the generation of pseudo-bipolar spindles. The increase in pseudo-bipolar spindles was reversed and an increase in the number of multi-polar spindles was observed upon expression of a constitutively active 14-3-3-binding-defective-mutant of cdc25C (S216A) in the 14-3-3γ knockdown cells. The increase in multi-polar spindle formation was associated with decreased cell viability and a decrease in tumor growth. Our findings uncover the molecular basis of regulation of centrosome duplication by 14-3-3γ and inhibition of tumor growth by premature activation of the mitotic program and the disruption of centrosome clustering.

The regulation of cell-cell adhesion is important for the processes of tissue formation and morphogenesis. Here we report that loss of 14-3-3γ leads to a decrease in cell-cell adhesion and a defect in the transport of plakoglobin (PG) and other desmosomal proteins to the cell border in HCT116 cells and in the mouse testis. 14-3-3γ binds to PG in a PKCμ dependent fashion resulting in microtubule dependent transport of PG to the border. Transport of PG to the border is dependent on the KIF5B/KLC1 complex. Knockdown of KIF5B in HCT116 cells or in the mouse testis, results in a phenotype similar to that observed with 14-3-3γ knockdown. Our results suggest that loss of 14-3-3γ leads to decreased desmosome formation and a decrease in cell-cell adhesion in vitro and in vivo in the mouse testis leading to defects in testis organization and spermatogenesis.

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INTRODUCTION: Peak expiratory flow rate (PEFR) is commonly used to monitor the progression of respiratory diseases as it gives good information about the status of airways. A good amount of research is going across the world to establish a local prediction equation. The joint task force of the American thoracic society and European Respiratory Society has promoted research in this regard. In India, data derived from the Caucasian population are still used for PEFR. OBJECTIVE: To verify the relationship between PEF levels and the variables age, sex, anthropometric and body surface area, and establish the regression equation for young Indian adults. METHODS:  A cross-sectional observational study was conducted in 15-25 years aged 1000 subjects from the Metropolitan region of Mumbai. Pearson’s correlation coefficient was used to understand the relation of anthropometric parameters and PEFR. Multivariate regression analysis was done for establishing a prediction equation (Alpha 5%).  RESULTS: Age and all anthropometric parameters were correlated with PEFR. The mean PEFR of the male population was 515 ml/sec, whereas, for females, it was 399 ml/sec, for PEFR highest correlation was observed with BSA (.696) followed by weight (.667), height (.630), age (.504) whereas BMI shown lowest correlation coefficient (.445). PEFR had the best significance with age, BSA, Height, and BMI. It had less significance with weight. In females, PEFR had the best significance with Height, weight, BMI, and Age. CONCLUSION: Gender-wise differences exist in PEFR. Hence gender-specific equations are needed for the estimation of PEFR.