NACA is a positive regulator of human erythroid-cell differentiation

Lopez, Sophie; Stuhl, L; Fichelson, Serge; Dubart‐Kupperschmitt, Anne; Arnaud, René; Galindo, J; Murati, Anne; Berda, Nicole; Dubreuil, Patrice; Gomez, Sophie

doi:10.1242/jcs.02295

Cited by 19 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, αNAC can function as a transcription coactivator St-Arnaud, 1998;St-Arnaud and Quelo, 1998;Yotov et al, 1998); it is a positive regulator in human erythroid-cell differentiation (Lopez et al, 2005) and a negative regulator in the proliferation, differentiation, and cytotoxic activation of CD8 (+) T cells (Al-Shanti et al, 2004;Al-Shanti and Aldahoodi, 2006). Furthermore, αNAC can interact with several disease related proteins (Goatley et al, 2002;Mossabeb et al, 2002;Li et al, 2005;Mittermann et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, isolated αNAC is a multiple functional protein taking part in transcription regulation St-Arnaud, 1998;St-Arnaud and Quelo, 1998;Yotov et al, 1998), cell proliferation, and differentiation (Al-Shanti et al, 2004;Lopez et al, 2005;Al-Shanti and Aldahoodi, 2006). Similarly, isolated βNAC (also called BTF3b) was initially identified as an alternative splicing isoform of the basic transcription factor (BTF3a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

et al. 2010

View full text Add to dashboard Cite

Nascent polypeptide associated complex (NAC) and its two isolated subunits, αNAC and βNAC, play important roles in nascent peptide targeting. We determined a 1.9 Å resolution crystal structure of the interaction core of NAC heterodimer and a 2.4 Å resolution crystal structure of αNAC NAC domain homodimer. These structures provide detailed information of NAC heterodimerization and αNAC homodimerization. We found that the NAC domains of αNAC and βNAC share very similar folding despite of their relative low identity of amino acid sequences. Furthermore, different electric charge distributions of the two subunits at the NAC interface provide an explanation to the observation that the heterodimer of NAC complex is more stable than the single subunit homodimer. In addition, we successfully built a βNAC NAC domain homodimer model based on homologous modeling, suggesting that NAC domain dimerization is a general property of the NAC family. These 3D structures allow further studies on structurefunction relationship of NAC.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Human umbilical vein endothelial cells (HUVEC) were isolated and cultivated as previously described [20]. CD34 positive cells were purified with magneted activated cell sorter (MACS) as already reported [21]. Hematopoietic cell lines were cultivated in RPMI medium supplemented with 10% foetal calf serum.…”

Section: Methodsmentioning

confidence: 99%

Nectin-4 is a new histological and serological tumor associated marker for breast cancer

et al. 2007

Self Cite

View full text Add to dashboard Cite

IntroductionBreast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research.Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma.MethodsExpression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR.Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test.ResultsNectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum Nectin-4 is also a marker of therapeutic efficiency and correlates, in 90% of cases, with clinical evolution.ConclusionNectin-4 is a new tumor-associated antigen for breast carcinoma. Nectin-4 is a new bio-marker whose use could help refine breast cancer taxonomy and improve patients' follow-up. Nectin-4 emerges as a potential target for breast cancer immunotherapy.

show abstract

“…1073/pnas.1013493107/-/DCSupplemental. also acts as a positive regulator of human erythroid cell differentiation (16,17).…”

mentioning

confidence: 99%

skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration

Park

Pierce

Drehle

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC −/− adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC −/− mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.C ardiogenesis is regulated in a temporally and spatially precise fashion by numerous signaling, transcriptional, and translational networks (1, 2). Epigenetic events, including posttranslational modification of histones, modulate the structure of chromatin and the accessibility of regulatory sequences to transcriptional activators and repressors. Acetylation of conserved lysine residues in histone tails by histone acetyltransferases stimulates chromatin relaxation and transcription, whereas deacetylation by histone deacetylases represses transcription (3). Methylation of lysine and arginine residues in histones affects chromatin conformation and either facilitates or inhibits transcription (4).Smyd1 is a muscle-restricted member of a family of chromatin remodeling proteins that contains both MYND and SET domains (5). The MYND domain coordinates protein-protein interactions to recruit a corepressor complex, and the SET domain commonly functions as a methyltransferase for histones or other proteins (6, 7). Targeted deletion of Smyd1 in mice results in a failure of ventricular cardiomyocyte maturation with ventricular hypoplasia, similar to cardiac phenotypes in embryos lacking Mef2c or Hand2 (dHAND) (5,8,9). Smyd1 is a direct transcriptional target of Mef2c and regulates the expression of Hand2 and Irx4, all of which function in a transcriptional network to control ventricular cardiomyocyte growth and differentiation (5, 10). Because of the early embryonic lethality of Smyd1 mutant mice, its role in skeletal muscle development remains unclear in mice. Knockdown of SmyD1a and SmyD1b expression in zebrafish embryos by morpholino antisense oligos resulted in a myofibril organization defect (11). Although Smyd1 may not bind DNA, it is likely recruited to muscle-specific target genes through physic...

show abstract

NACA is a positive regulator of human erythroid-cell differentiation

Cited by 19 publications

References 29 publications

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

Crystal structures of NAC domains of human nascent polypeptide-associated complex (NAC) and its αNAC subunit

Nectin-4 is a new histological and serological tumor associated marker for breast cancer

skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration

Contact Info

Product

Resources

About