Academic Journal
Inactivation of the polycomb group protein Ring1B unveils an antiproliferative role in hematopoietic cell expansion and cooperation with tumorigenesis associated with Ink4a deletion
| العنوان: | Inactivation of the polycomb group protein Ring1B unveils an antiproliferative role in hematopoietic cell expansion and cooperation with tumorigenesis associated with Ink4a deletion |
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| المؤلفون: | Calés, Carmela, Román-Trufero, Mónica, Pavón, Leticia, Serrano, Iván, Melgar, Teresa |
| بيانات النشر: | American Society for Microbiology |
| سنة النشر: | 2008 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | 11 pages, 7 figures.-- et al. ; Polycomb group (PcG) proteins act as positive regulators of cell proliferation. Ring1B is a PcG gene essential for embryonic development, but its contribution to cell turnover in regenerating tissues in not known. Here, we have generated a conditional mouse mutant line to study the Ring1B role in adult hematopoiesis. Mutant mice developed a hypocellular bone marrow that paradoxically contained an enlarged, hyperproliferating compartment of immature cells, with an intact differentiation potential. These alterations were associated with differential upregulation of cyclin D2, which occurred in all mutant bone marrow cells, and of p16(Ink4a), observed only in the differentiated compartment. Concurrent inactivation of Ink4a rescued the defective proliferation of maturing cells but did not affect the hyperproliferative activity of progenitors and resulted in a shortening of the onset of lymphomas induced by Ink4a inactivation. These data show that Ring1B restricts the progenitors' proliferation and promotes the proliferation of their maturing progeny by selectively altering the expression pattern of cell cycle regulators along hematopoietic differentiation. The novel antiproliferative role of Ring1B's downregulation of a cell cycle activator may play an important role in the tight control of hematopoietic cell turnover. ; T.M. and M.R-T. were recipients of FPI and FPU fellowships, respectively, from the Ministerio de Educación y Ciencia. This work was supported by grants from the Fundación Médica Mutua Madrileña (C.C.), Plan Nacional de Investigacion Científica BFU2005-03651 (C.C.) and SAF2004-06952-CO2-01 (M.V.), the OncoCycle program from the Comunidad de Madrid (M.V.), and in part by a grant of the Genome Network Project from the Ministry of Education Culture, Sports, Science and Technology of the Japanese Government (H.K.). ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 495084 bytes; application/pdf |
| اللغة: | English |
| Relation: | http://dx.doi.org/10.1128/MCB.01136-07; http://hdl.handle.net/10261/25055 |
| DOI: | 10.1128/MCB.01136-07 |
| الاتاحة: | http://hdl.handle.net/10261/25055 https://doi.org/10.1128/MCB.01136-07 |
| Rights: | open |
| رقم الانضمام: | edsbas.E121F6E9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1128/MCB.01136-07 |
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