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1.
Cell Mol Immunol ; 20(3): 277-291, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36631557

RESUMEN

Upon recognition of foreign antigens, naïve B cells undergo rapid activation, growth, and proliferation. How B-cell growth and proliferation are coupled with activation remains poorly understood. Combining CRISPR/Cas9-mediated functional analysis and mouse genetics approaches, we found that Dhx33, an activation-induced RNA helicase, plays a critical role in coupling B-cell activation with growth and proliferation. Mutant mice with B-cell-specific deletion of Dhx33 exhibited impaired B-cell development, germinal center reactions, plasma cell differentiation, and antibody production. Dhx33-deficient B cells appeared normal in the steady state and early stage of activation but were retarded in growth and proliferation. Mechanistically, Dhx33 played an indispensable role in activation-induced upregulation of ribosomal DNA (rDNA) transcription. In the absence of Dhx33, activated B cells were compromised in their ability to ramp up 47S ribosomal RNA (rRNA) production and ribosome biogenesis, resulting in nucleolar stress, p53 accumulation, and cellular death. Our findings demonstrate an essential role for Dhx33 in coupling B-cell activation with growth and proliferation and suggest that Dhx33 inhibition is a potential therapy for lymphoma and antibody-mediated autoimmune diseases.


Asunto(s)
ARN Ribosómico , Animales , Ratones , Ciclo Celular , Proliferación Celular , ARN Ribosómico/genética , Regulación hacia Arriba
2.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 7): m910, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21836896

RESUMEN

In the crystal structure of the centrosymmetric binuclear title complex, [Ni(2)(C(12)H(8)N(2)O(2)S)(2)(CH(3)OH)(4)], there are inter-molecular O-H⋯O, O-H⋯N and O-H⋯S hydrogen bonds. These help to stabilize the structure and link the mol-ecules, forming a three-dimensional network structure. The Ni(2+) cation exists in a slightly distorted octahedral NiNO(5) coordination environment. The thio-phene rings are disordered over two equivalent conformations with occupancies of 0.881 (3) and 0.119 (3).

3.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 4): o920, 2010 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-21580730

RESUMEN

In the crystal structure of the title compound, C(11)H(15)N(3)O(3), mol-ecules are linked into a chain by inter-molecular N-H⋯O hydrogen bonds.

4.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 10): o2367, 2009 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-21577833

RESUMEN

The title compound, C(12)H(9)N(2)O(2) (+)·Cl(-)·2H(2)O, exhibits a layered structure which is stabilized by inter-molecular O-H⋯O, O-H⋯Cl(-) and N(+)-H⋯Cl(-) hydrogen bonds, and π-π inter-actions (centroid-centroid distances = 3.654 and 3.583 Å). The distances between the molecules are 3.371 and 3.294 Å.

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