Point mutation in AML1 disrupts subnuclear targeting, prevents myeloid differentiation, and effects a transformation-like phenotype.
AuthorsVradii D, Zaidi SK, Lian JB, van Wijnen AJ, Stein JL, Stein GS,
JournalProc Natl Acad Sci U S A
PubMed ID15870195
'The multifunctional C terminus of the hematopoietic AML1 transcription factor interacts with coregulatory proteins, supports the convergence and integration of physiological signals, and contains the nuclear matrix targeting signal, the protein motif that is necessary and sufficient to target AML1 to subnuclear sites. The (8;21) chromosomal translocation, which replaces the ... More
The BRCA-1 binding protein BRAP2 is a novel, negative regulator of nuclear import of viral proteins, dependent on phosphorylation flanking the nuclear localization signal.
AuthorsFulcher AJ, Roth DM, Fatima S, Alvisi G, Jans DA
JournalFASEB J
PubMed ID20040518
'This study describes for the first time the ability of the novel BRCA1-binding protein 2 (BRAP2) to inhibit the nuclear import of specific viral proteins dependent on phosphorylation. Ectopic expression of BRAP2 in transfected African green monkey kidney COS-7 cells was found to significantly reduce nuclear localization signal (NLS)-dependent nuclear ... More
Two distinct Fas-activated signaling pathways revealed by an antitumor drug D609.
AuthorsZhang L, Shimizu S, Tsujimoto Y,
JournalOncogene
PubMed ID15846303
'During the process of death receptor-mediated apoptosis, Bid is cleaved by activated caspase-8, and then cleaved Bid conveys apoptotic signals to the mitochondria by activating Bax/Bak. In the present study, we found that D609 (an antitumor drug with multiple activities) blocks Fas-induced apoptosis. D609 did not interfere with activation of ... More
JNJ-26481585, a novel
AuthorsArts J, King P, Mariën A, Floren W, Beliën A, Janssen L, Pilatte I, Roux B, Decrane L, Gilissen R, Hickson I, Vreys V, Cox E, Bol K, Talloen W, Goris I, Andries L, Du Jardin M, Janicot M, Page M, van Emelen K, Angibaud P,
JournalClin Cancer Res
PubMed ID19861438
Histone deacetylase (HDAC) inhibitors have shown promising clinical activity in the treatment of hematologic malignancies, but their activity in solid tumor indications has been limited. Most HDAC inhibitors in clinical development only transiently induce histone acetylation in tumor tissue. Here, we sought to identify a ... More
Growth differentiation factor-5 promotes brown adipogenesis in systemic energy expenditure.
AuthorsHinoi E, Nakamura Y, Takada S, Fujita H, Iezaki T, Hashizume S, Takahashi S, Odaka Y, Watanabe T, Yoneda Y,
Journal
PubMed ID24062245
Although growth differentiation factor-5 (GDF5) has been implicated in skeletal development and joint morphogenesis in mammals, little is known about its functionality in adipogenesis and energy homeostasis. Here, we show a critical role of GDF5 in regulating brown adipogenesis for systemic energy expenditure in mice. GDF5 expression was preferentially upregulated ... More
Dual regulation of the transcriptional activity of Nrf1 by ß-TrCP- and Hrd1-dependent degradation mechanisms.
AuthorsTsuchiya Y, Morita T, Kim M, Iemura S, Natsume T, Yamamoto M, Kobayashi A
JournalMol Cell Biol
PubMed ID21911472
A growing body of evidence suggests that Nrf1 is an inducible transcription factor that maintains cellular homeostasis. Under physiological conditions, Nrf1 is targeted to the endoplasmic reticulum (ER), implying that it translocates into the nucleus in response to an activating signal. However, the molecular mechanisms by which the function of ... More