MiR-210 and miR-155 are Upregulated in CFBE Cells and Involved in Fe-S Protein Assembly via ISCU Downregulation as well as HO-1 Expression via BACH1.

Pneumologie ◽  
2015 ◽  
Vol 69 (07) ◽  
Author(s):  
S Chillappagari ◽  
V Garapati ◽  
P Mahavadi ◽  
O Stehling ◽  
R Lill ◽  
...  
Keyword(s):  
2005 ◽  
Vol 25 (24) ◽  
pp. 10833-10841 ◽  
Author(s):  
Janneke Balk ◽  
Daili J. Aguilar Netz ◽  
Katharina Tepper ◽  
Antonio J. Pierik ◽  
Roland Lill

ABSTRACT The assembly of cytosolic and nuclear iron-sulfur (Fe/S) proteins in yeast is dependent on the iron-sulfur cluster assembly and export machineries in mitochondria and three recently identified extramitochondrial proteins, the P-loop NTPases Cfd1 and Nbp35 and the hydrogenase-like Nar1. However, the molecular mechanism of Fe/S protein assembly in the cytosol is far from being understood, and more components are anticipated to take part in this process. Here, we have identified and functionally characterized a novel WD40 repeat protein, designated Cia1, as an essential component required for Fe/S cluster assembly in vivo on cytosolic and nuclear, but not mitochondrial, Fe/S proteins. Surprisingly, Nbp35 and Nar1, themselves Fe/S proteins, could assemble their Fe/S clusters in the absence of Cia1, demonstrating that these components act before Cia1. Consequently, Cia1 is involved in a late step of Fe/S cluster incorporation into target proteins. Coimmunoprecipitation assays demonstrated a specific interaction between Cia1 and Nar1. In contrast to the mostly cytosolic Nar1, Cia1 is preferentially localized to the nucleus, suggesting an additional function of Cia1. Taken together, our results indicate that Cia1 is a new member of the cytosolic Fe/S protein assembly (CIA) machinery participating in a step after Nbp35 and Nar1.


2012 ◽  
Vol 287 (15) ◽  
pp. 12365-12378 ◽  
Author(s):  
Daili J. A. Netz ◽  
Antonio J. Pierik ◽  
Martin Stümpfig ◽  
Eckhard Bill ◽  
Anil K. Sharma ◽  
...  

The essential P-loop NTPases Cfd1 and Nbp35 of the cytosolic iron-sulfur (Fe-S) protein assembly machinery perform a scaffold function for Fe-S cluster synthesis. Both proteins contain a nucleotide binding motif of unknown function and a C-terminal motif with four conserved cysteine residues. The latter motif defines the Mrp/Nbp35 subclass of P-loop NTPases and is suspected to be involved in transient Fe-S cluster binding. To elucidate the function of these two motifs, we first created cysteine mutant proteins of Cfd1 and Nbp35 and investigated the consequences of these mutations by genetic, cell biological, biochemical, and spectroscopic approaches. The two central cysteine residues (CPXC) of the C-terminal motif were found to be crucial for cell viability, protein function, coordination of a labile [4Fe-4S] cluster, and Cfd1-Nbp35 hetero-tetramer formation. Surprisingly, the two proximal cysteine residues were dispensable for all these functions, despite their strict evolutionary conservation. Several lines of evidence suggest that the C-terminal CPXC motifs of Cfd1-Nbp35 coordinate a bridging [4Fe-4S] cluster. Upon mutation of the nucleotide binding motifs Fe-S clusters could no longer be assembled on these proteins unless wild-type copies of Cfd1 and Nbp35 were present in trans. This result indicated that Fe-S cluster loading on these scaffold proteins is a nucleotide-dependent step. We propose that the bridging coordination of the C-terminal Fe-S cluster may be ideal for its facile assembly, labile binding, and efficient transfer to target Fe-S apoproteins, a step facilitated by the cytosolic iron-sulfur (Fe-S) protein assembly proteins Nar1 and Cia1 in vivo.


2008 ◽  
Vol 28 (17) ◽  
pp. 5517-5528 ◽  
Author(s):  
Oliver Stehling ◽  
Daili J. A. Netz ◽  
Brigitte Niggemeyer ◽  
Ralf Rösser ◽  
Richard S. Eisenstein ◽  
...  

ABSTRACT The maturation of cytosolic iron-sulfur (Fe/S) proteins in mammalian cells requires components of the mitochondrial iron-sulfur cluster assembly and export machineries. Little is known about the cytosolic components that may facilitate the assembly process. Here, we identified the cytosolic soluble P-loop NTPase termed huNbp35 (also known as Nubp1) as an Fe/S protein, and we defined its role in the maturation of Fe/S proteins in HeLa cells. Depletion of huNbp35 by RNA interference decreased cell growth considerably, indicating its essential function. The deficiency in huNbp35 was associated with an impaired maturation of the cytosolic Fe/S proteins glutamine phosphoribosylpyrophosphate amidotransferase and iron regulatory protein 1 (IRP1), while mitochondrial Fe/S proteins remained intact. Consequently, huNbp35 is specifically involved in the formation of extramitochondrial Fe/S proteins. The impaired maturation of IRP1 upon huNbp35 depletion had profound consequences for cellular iron metabolism, leading to decreased cellular H-ferritin, increased transferrin receptor levels, and higher transferrin uptake. These properties clearly distinguished huNbp35 from its yeast counterpart Nbp35, which is essential for cytosolic-nuclear Fe/S protein assembly but plays no role in iron regulation. huNbp35 formed a complex with its close homologue huCfd1 (also known as Nubp2) in vivo, suggesting the existence of a heteromeric P-loop NTPase complex that is required for both cytosolic Fe/S protein assembly and cellular iron homeostasis.


2010 ◽  
Vol 6 (10) ◽  
pp. 700-701 ◽  
Author(s):  
Patricia C Dos Santos ◽  
Dennis R Dean
Keyword(s):  

Neurology ◽  
2015 ◽  
Vol 84 (7) ◽  
pp. 659-667 ◽  
Author(s):  
A. Lossos ◽  
C. Stumpfig ◽  
G. Stevanin ◽  
M. Gaussen ◽  
B.-E. Zimmerman ◽  
...  

2016 ◽  
Vol 473 (14) ◽  
pp. 2073-2085 ◽  
Author(s):  
Daili J.A. Netz ◽  
Heide M. Genau ◽  
Benjamin D. Weiler ◽  
Eckhard Bill ◽  
Antonio J. Pierik ◽  
...  

The essential protein Dre2 uses iron–sulfur (Fe–S) clusters to transfer electrons for cytosolic Fe–S protein biogenesis. Biochemical, cell biological and spectroscopic approaches demonstrate that recombinant Dre2 binds oxygen-labile [2Fe–2S] and [4Fe–4S] clusters at two conserved C-terminal motifs with four cysteine residues each.


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