Biochemical Characterization of the NF-Y Transcription Factor Complex during B Lymphocyte Development

Ra, Currie

doi:10.1074/jbc.273.29.18220

Cited by 19 publications

(16 citation statements)

References 57 publications

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“…However, progression to the plasma B-cell stage after being stimulated with foreign antigens, various mitogens, and T-cell factors results in the uniform repression of the expression of all class II genes at the transcriptional level (46). NF-Y is associated with the protein cofactor PC4, which might play an important role in the NF-Y -mediated transcriptional control of the class II genes in B lymphocytes (47). In addition to the adenocarcinoma tissues, cyclin B2 was also found in the germinal centers containing mainly B lymphocytes in the mucosal lymph follicles and lymph node in nontumor tissues.…”

Section: Discussionmentioning

confidence: 99%

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

Park¹,

Yu²,

Kim

et al. 2007

Clinical Cancer Research

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Purpose: Cyclin B2, a G 2 -M cyclin, is overexpressed in colorectal adenocarcinomas compared with the normal mucosa. This study examined the level of cyclin B2 overexpression according to the histologic findings and investigated the mechanism(s) and clinical implications of cyclin B2 overexpression in colorectal adenocarcinomas. Experimental Design: The immunoreactivity of the polyclonal antibodies to cyclin B2 was determined in colorectal cancer cells. The transcriptional regulation of cyclin B2 by NF-Y was analyzed using an in vitro transfection assay and an in vivo chromatin immunoprecipitation assay. The proliferative activity of the colorectal cancer cells in relation to cyclin B2 overexpression was further examined. Results: The cytoplasmic distribution of cyclin B2 immunoreactivity was positive in 42 of 65 (64.6%) cases of colorectal adenocarcinoma, and the level was similar regardless of the histologic type. A dominant-negative form of NF-YA effectively inhibited the cyclin B2 promoter activity, and NF-Y was found to bind three conserved CCAAT boxes in the cyclin B2 promoter in colorectal adenocarcinoma cells.Tumor cells with a higher functional cyclin B2 activity grew faster than those with a lower activity. Furthermore, there was a correlation between the cells showing immunoreactivity to cyclin B2 and those containing the proliferating cell nuclear antigen, a G 1 -S cyclin, which is also downstream of NF-Y in colorectal adenocarcinoma cells. Conclusions: Cyclin B2 seems to be a molecular marker of a colorectal adenocarcinoma and that its up-regulation and coordinate expression of the other cell cycle^related genes by NF-Y might contribute to tumor cell proliferation by accelerating cell cycle progression.Mitosis is induced by the activation of the M-phasepromoting factor, which is a protein kinase whose principal subunits are p34 cdc2 and cyclin B. Cyclin B is a regulatory subunit that varies in abundance throughout the cell cycle (1). The metaphase to anaphase transition marks the end of mitosis and is induced by the degradation of cyclin B, which in turn leads to the inactivation of M-phase -promoting factor. As the cell cycle progresses, cyclin B begins to accumulate when the cell enters the interphase, which is followed by the reactivation of M-phase -promoting factor and another round of mitosis. Therefore, the B-type cyclins are the primary mitotic cyclins, although several yeast B-type cyclins have been reported to function earlier in the cell cycle, particularly in the S phase (2, 3). There are two mammalian B-type cyclins, cyclins B1 and B2, which differ in their NH 2 termini but have 57% similarity (4 -6). Cyclins B1 and B2 are coexpressed in most dividing cells and, in association with cdc2, play a role in entering the G 2 -M phase, although their subcellular localization differs (7). Cyclin B1 is primarily cytoplasmic but constantly shuttles between the nucleus and the cytoplasm during the interphase. At the end of the prophase, cyclin B1 rapidly translocates to the nucleus (8, 9)...

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Section: Discussionmentioning

confidence: 99%

NF-Y–Dependent Cyclin B2 Expression in Colorectal Adenocarcinoma

Park¹,

Yu²,

Kim

et al. 2007

Clinical Cancer Research

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“…All these effects are strictly dependent on the presence of the CCAAT boxes. NF-Y interacts with hGCN5 (Currie, 1998), and NF-YB is acetylated in Xenopus by p300, but the consequences of this modification have not been addressed (Li et al, 1998). In vivo studies by chromatin immunoprecipitation on cell cycleregulated promoters highlighted the dynamic behavior of NF-Y and HATs binding during cell cycle progression Salsi et al, 2003;Di Agostino et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Posttranslational Regulation of NF-YA Modulates NF-Y Transcriptional Activity

Manni¹,

Caretti

Artuso³

et al. 2008

MBoC

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Here we show that the levels of NF-YA protein are regulated posttranslationally by ubiquitylation and acetylation. A NF-YA protein carrying four mutated lysines in the C-terminal domain is more stable than the wild-type form, indicating that these lysines are ubiquitylated Two of the lysines are acetylated in vitro by p300, suggesting a competition between ubiquitylation and acetylation of overlapping residues. Interestingly, overexpression of a degradation-resistant NF-YA protein leads to sustained expression of mitotic cyclin complexes and increased cell proliferation, indicating that a tight regulation of NF-YA levels contributes to regulate NF-Y activity. INTRODUCTIONThe CCAAT-binding transcription factor NF-Y is a heteromeric protein composed of three subunits, NF-YA, -YB, and -YC, all necessary for CCAAT binding (Mantovani, 1999). The NF-Y complex supports the basal transcription of a class of regulatory genes responsible for cell cycle progression, among which are mitotic cyclin complexes (Zwicker et al., 1995a,b;Bolognese et al., 1999;Farina et al., 1999;Korner et al., 2001;Gurtner et al., 2003Gurtner et al., , 2008Di Agostino et al., 2006). Knock-out mice clearly demonstrates that NF-Y dependent transcription is essential during early mouse development (Bhattacharya et al., 2003). The NF-Y function in proliferation is also demonstrated by the inhibition of DNA binding by endogenous NF-Y, resulting in retardation of fibroblast growth, which is brought about by overexpression of a dominant negative mutant of the NF-YA subunit (Hu and Maity, 2000). The differential expression of NF-YA, altering NF-Y CCAAT-binding activity, has been observed in several cell lines and tissues both during cell cycle progression and under specific conditions. NF-YA expression is modulated during the cell cycle, being high in G1, further increasing in S, and then decreasing in the G2/M phase (Bolognese et al., 1999). Reduction of NF-YA expression has been reported in IMR-90 fibroblasts after serum deprivation (Chang et al., 1994) and in human monocytes (Marziali et al., 1997). The NF-YA protein is not expressed in terminally differentiated C2C12 muscle cells and adult skeletal muscle tissues (Farina et al., 1999;Gurtner et al., 2003Gurtner et al., , 2008. These observations show that levels of NF-YA dictate the function of the NF-Y complex. Interestingly, control of NF-YA accumulation is posttranscriptional, because NF-YA mRNA is relatively constant in growing and differentiated cells (Bolognese et al., 1999;Farina et al., 1999). Yet, the mechanisms regulating the stability of the NF-YA protein remain unknown.The covalent addition of ubiquitin, a 76-amino acid protein highly conserved among eukaryotes, is an increasingly common posttranslation modification that controls both the expression and the activity of numerous proteins in the eukaryotic cell (Hershko and Ciechanover, 1998;Ciechanover et al., 2000). The ubiquitin-proteasome pathway is composed of the ubiquitin-conjugating system and the 26S proteasome; the latter contain...

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“…Its three subunits, YA, YB, and YC, are collectively required for NF-Y DNA-binding activity (12); NF-Y has been detected in almost all cell types, which was initially construed to mean that it exemplified an immutable, constitutive transcription factor; however, more recently it has been demonstrated that NF-Y's affinity for DNA alters over B-cell lifespan, potentially offering a means to fine-tune the subset of its target genes expressed during development (13) senescence (14,15), and differentiation (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%