Posttranscriptional Modulation of Gene Expression in Cultured Rat Hepatocytes

We previously isolated HBP1 as a target of the retinoblastoma (RB) and p130 family members and as the first of the HMG box transcriptional repressors. Our subsequent work demonstrated that HBP1 coordinates differentiation in cell culture models. In the present study, we show that HBP1 regulates proliferation in a differentiated tissue of an animal. Using transgenic mice in which HBP1 expression was specifically increased in hepatocytes under control of the transthyretin promoter, we determined the impact of HBP1 on synchronous cell cycle reentry following partial hepatectomy. Modest overexpression of HBP1 yielded a detectable cell cycle phenotype. Following a mitogenic stimulus induced by two-thirds partial hepatectomy, mice expressing the HBP1 transgene showed a 10-to 12-h delay in progression through G 1 to the peak of S phase. There was a concomitant delay in mid-G 1 events, such as the induction of cyclin E. While the delay in G 1 and S phases correlated with the slight overexpression of transgenic HBP1, the level of the endogenous HBP1 protein itself declined in S phase. In contrast, the onset of the immediate-early response following partial hepatectomy was unchanged in HBP1 transgenic mice. This observation indicated that the observed delay in S phase did not result from changes in signaling pathways leading into the G 0 -to-G 1 transition. Finally, transgenic mice expressing a mutant HBP1 lacking the N-terminal RB interacting domain showed a stronger S-phase response following partial hepatectomy. These results provide the first evidence that HBP1 can regulate cell cycle progression in differentiated tissues.

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HMG Box Transcriptional Repressor HBP1 Maintains a Proliferation Barrier in Differentiated Liver Tissue

Shih

Xiu

Berasi

et al. 2001

Molecular and Cellular Biology

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Diverse Patterns of Expression of the Cytochrome c Oxidase Subunit I Gene and Unassigned Reading Frames 4 and 5 During the Life Cycle of Trypanosoma brucei

Jasmer¹,

Feagin²,

Stuart³

1985

Molecular and Cellular Biology

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Transcription of a maxicircle segment from Trypanosoma brucei 164 that contains nucleotide (nt) sequences corresponding to cytochrome c oxidase subunit I (COI) and unassigned reading frames (URFs) 4 and 5 of other mitochondrial systems was investigated. Two major transcripts that differ in size by ca. 200 nt map to each of the COI and URF4 genes, while a single major transcript maps to URF5. In total RNA, the larger COI transcript is more abundant in procyclic forms (PFs) than in bloodstream forms (BFs), the smaller COI and both URF4 transcripts have similar abundances in both forms, and the single URF5 transcript is more abundant in BF than PF. These patterns of expression differ in poly(A)+ RNA as a result of a higher proportion of poly(A)+ mitochondrial transcripts in PFs than in BFs. In addition, small (300- to 500-nt) RNAs that are transcribed from C-rich sequences located between putative protein-coding genes also exhibit diverse patterns of expression between life cycle stages and differences in polyadenylation in PFs compared with BFs. These observations suggest that multiple processes regulate the differential expression of mitochondrial genes in T. brucei.

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Eel Electric Organ: Hyperexpressing Calmodulin System

Munjaal¹,

Connor²,

Turner³

et al. 1986

Molecular and Cellular Biology

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The electroplax of the electric eel Electrophorus electricus is the most abundant source of the calcium-binding protein calmodulin. The electroplax has 250 times the amount of calmodulin and its mRNA than eel skeletal muscle. Our data suggest that there is no major difference in gene copies, the degree of methylation, or genome rearrangement of the calmodulin gene in DNAs from eel electroplax and muscle. Differences in the calmodulin-binding proteins in electroplax and muscle suggest a differential role for the functional expression of calmodulin in cellular regulation.

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Posttranscriptional Modulation of Gene Expression in Cultured Rat Hepatocytes

Cited by 4 publications

References 30 publications

HMG Box Transcriptional Repressor HBP1 Maintains a Proliferation Barrier in Differentiated Liver Tissue

HMG Box Transcriptional Repressor HBP1 Maintains a Proliferation Barrier in Differentiated Liver Tissue

Diverse Patterns of Expression of the Cytochrome c Oxidase Subunit I Gene and Unassigned Reading Frames 4 and 5 During the Life Cycle of Trypanosoma brucei

Eel Electric Organ: Hyperexpressing Calmodulin System

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