CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin

CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-κB signalling. Here we show that CYLD controls cell growth and division at the G1/S-phase as well as cytokinesis by associating with α-tubulin and microtubules through its CAP-Gly domains. Translocation of activated CYLD to the perinuclear region of the cell is achieved by an inhibitory interaction of CYLD with histone deacetylase-6 (HDAC6) leading to an increase in the levels of acetylated α-tubulin around the nucleus. This facilitates the interaction of CYLD with Bcl-3, leading to a significant delay in the G1-to-S-phase transition. Finally, CYLD also interacts with HDAC6 in the midbody where it regulates the rate of cytokinesis in a deubiquitinase-independent manner. Altogether these results identify a mechanism by which CYLD regulates cell proliferation at distinct cell-cycle phases

The use of NDVI and its Derivatives for Monitoring Lake Victoria’s Water Level and Drought Conditions

Normalized Difference Vegetation Index (NDVI), which is a measure of vegetation vigour, and lake water levels respond variably to precipitation and its deficiency. For a given lake catchment, NDVI may have the ability to depict localized natural variability in water levels in response to weather patterns. This information may be used to decipher natural from unnatural variations of a given lake’s surface. This study evaluates the potential of using NDVI and its associated derivatives (VCI (vegetation condition index), SVI (standardised vegetation index), AINDVI (annually integrated NDVI), green vegetation function (F g ), and NDVIA (NDVI anomaly)) to depict Lake Victoria’s water levels. Thirty years of monthly mean water levels and a portion of the Global Inventory Modelling and Mapping Studies (GIMMS) AVHRR (Advanced Very High Resolution Radiometer) NDVI datasets were used. Their aggregate data structures and temporal co-variabilities were analysed using GIS/spatial analysis tools. Locally, NDVI was found to be more sensitive to drought (i.e., responded more strongly to reduced precipitation) than to water levels. It showed a good ability to depict water levels one-month in advance, especially in moderate to low precipitation years. SVI and SWL (standardized water levels) used in association with AINDVI and AMWLA (annual mean water levels anomaly) readily identified high precipitation years, which are also when NDVI has a low ability to depict water levels. NDVI also appears to be able to highlight unnatural variations in water levels. We propose an iterative approach for the better use of NDVI, which may be useful in developing an early warning mechanisms for the management of lake Victoria and other Lakes with similar characteristics

The Anti-Proliferative Effects of the CHFR Depend on the Forkhead Associated Domain, but not E3 Ligase Activity Mediated by Ring Finger Domain

The CHFR protein comprises fork head associated- (FHA) and RING-finger (RF) domain and is frequently downregulated in human colon and gastric cancers up to 50%. The loss of CHFR mRNA expression is a consequence of promoter methylation, suggesting a tumor suppressor role for this gene in gastrointestinal carcinogenesis. In terms of the biological functions of CHFR, it has been shown to activate cell cycle checkpoint when cells are treated with microtubule depolymerizing agents. Furthermore, CHFR was reported to have E3 ligase activity and promote ubiquitination and degradation of oncogenic proteins such as Aurora A and polo-like kinase 1. However, molecular pathways involved in the tumor suppressive function of CHFR are not yet clear since the two established roles of this protein are likely to inhibit cell growth. In this study, we have identified that the FHA domain of CHFR protein is critical for growth suppressive properties, whereas the RF and cysteine rich domains (Cys) are not required for this function. In contrast, the RF and Cys domains are essential for E3 ligase activity of CHFR. By the use of a cell cycle checkpoint assay, we also confirmed that the FHA domain of CHFR plays an important role in initiating a cell cycle arrest at G2/M, indicating a functional link exists between the anti-proliferative effects and checkpoint function of this tumor suppressor protein via this domain. Collectively, our data show that the checkpoint function of the FHA domain of CHFR is a core component of anti-proliferative properties against the gastrointestinal carcinogenesis