title: p53 Represses transcription of RING finger LIM domain-binding protein RLIM through Sp1.
abstract: RLIM acts as a negative regulator of LIM-Homeodomain proteins either by recruiting Sin3A/Histone Deacetylase (HDAC) co-repressor complex or through degradation of CLIM coactivator, thus playing an important role in embryonic development. Recent studies by different research groups have shown that RLIM acts as an X-encoded, dose-dependent inducer of X chromosome inactivation in mouse embryonic stem cells. However, until now, very little is known about the expression regulation of RLIM gene, and we tried to study the transcriptional regulation of RLIM gene. In the present study, we identified RLIM as a novel target of p53 and demonstrated that p53 repressed both mRNA and protein levels of RLIM. Expression of wild type p53, but not p53 mutants, led to repression of the RLIM promoter activity. We further identified four putative Sp1 elements (S1 to S4) on the RLIM promoter that are essential for p53-mediated repression of RLIM. Although p53 does not directly bind to the RLIM promoter, it physically interacts with and prevents the binding of Sp1 to the RLIM promoter. Thus, RLIM is a novel target of p53, and p53 exerts its inhibitory effect on RLIM expression by interfering with Sp1-mediated transcriptional activation on RLIM. Our results provided data to enlarge the knowledge of transcriptional regulation of RLIM and suggested a new pathway by which physiological and pathological activators of p53 may affect development.
authors: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, PR China.
authors: Xiangtao
authors: X
authors: Kong
authors: Bo
authors: B
authors: Peng
authors: Yang
authors: Y
authors: Yang
authors: Pingzhao
authors: P
authors: Zhang
authors: Bo
authors: B
authors: Qin
authors: Dingding
authors: D
authors: Han
authors: Chenji
authors: C
authors: Wang
authors: Yongjun
authors: Y
authors: Dang
authors: Jun O
authors: JO
authors: Liu
authors: Long
authors: L
authors: Yu
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D017422:Sequence Analysis, DNA; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C492370:RLIM protein, human; D044767:Ubiquitin-Protein Ligases
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