To degrade LDs that are enriched with CE, however, lysosomal acid lipase, which has CE hydrolytic activity, may be involved, as it is for degradation of cholesterolloaded macrophages. For LDs containing CE and TG in comparable amounts, CE hydrolysis may be a prerequisite for effective TG degradation because CE may surround the TG core, forming concentric Perifosine layers on the surface. In this context, it is notable that the deficiency of lysosomal acid lipase that characterizes Wolman disease manifests as an accumulation of CE as well as TG. It was surprising that, upon treatment with translation inhibitors, TIP47 was recruited to the CE-rich LDs even though the total amount of TIP47 decreased drastically. TIP47 was previously shown to be recruited to TG-rich LDs induced by unsaturated fatty acids, but in such cases the overall expression of TIP47 also increased. The present result Carfilzomib indicates that TIP47 recruitment to LDs does not depend on the increased expression of TIP47 or on the composition of the lipid esters in LDs; rather, it is directly related to the increment of lipid esters. On the other hand, the increased recruitment of TIP47 to LDs should reduce TIP47 in the soluble cytoplasmic fraction, especially when the total amount is downregulated. Although the non-LD function of TIP47 remains controversial, it must be determined whether any result seen in the presence of translation inhibitors can be explained by a decrease in TIP47 in the cytoplasm. The phenomena observed in the present study need to be taken into account in interpreting experimental results obtained using translation inhibitors. Yet the implications of this study are not limited to such artificial conditions, given that, in cells exposed to various stresses, protein synthesis is suppressed and LDs increase. LDs that increase in cultured cells under ER stress are enriched with CE. The detailed mechanism underlying CE-rich LD formation as well as the impact of this process are worthy of further studies in this context. Cyclin dependent kinases are a group of protein kinases which regulate different stages of the eukaryotic cell cycle. CDKs are also involved in the control of gene transcription, the processes that integrate extracellular and intracellular signals for the coordination of the cell cycle in response to environmental change, and apoptosis. Activation of CDKs usually occurs via phosphorylation of specific threonine residues by the CDKactivating kinase and binding to a cyclin protein. CDK4 plays a central role in the regulation of the G0-G1 phase of the cell and is required for the G1/S phase transition. CDK4 inactivates the retinoblastoma protein by phosphorylation. pRb is a negative regulator of the E2F family of transcription factors, hence phosphorylation of pRb results in the release of transcription factors which activate the expression of the S-phase genes. This process enables the cell to pass through the restriction point and results in the onset of the S-phase. Cell cycle regulators are frequently mutated in human cancers and due to their central role in G1 regulation CDKs offer attractive targets for therapeutic inhibition. The work of Yu et al. and Landis et al. suggests that inhibition of CDK4 might benefit patients with ErbB-2 initiated breast cancers. The CDK4/CyclinD1 complex as an anti-cancer drug target has been further validated in MCF-7 breast cancer cells. More than 20 small molecule inhibitors for CDKs are in clinical trials. For example, Flavopiridol is in clinical development for the treatment of different metastatic cancers. R-Roscovitine inhibits CDK2, CDK7 and CDK9 and is also in clinical trials.