Cloning and Expression of a Novel Nuclear Matrix-associated Protein That Is Regulated during the Retinoic Acid-induced Neuronal Differentiation

Cheung, William M.W.; Chu, Apple H.; Chu, Patrick; Ip, Nancy Y.

doi:10.1074/jbc.m010802200

Cited by 33 publications

(40 citation statements)

References 40 publications

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“…This TAP-DTL was expressed at a comparable level to the endogenous DTL and showed the appropriate nuclear localization ( Fig. 3A; Cheung et al 2001; data not shown). We affinity-purified TAP-DTL, or the TAP control protein, and then screened for DDB1 and CUL4A by immunoblotting (Fig.…”

Section: Dtl Associates With the Cul4a-ddb1 E3 Ubiquitin Ligasementioning

confidence: 83%

DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint

Sansam¹,

Shepard²,

Lai³

et al. 2006

Genes Dev.

147

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Checkpoint genes maintain genomic stability by arresting cells after DNA damage. Many of these genes also control cell cycle events in unperturbed cells. By conducting a screen for checkpoint genes in zebrafish, we found that dtl/cdt2 is an essential component of the early, radiation-induced G2/M checkpoint. We subsequently found that dtl/cdt2 is required for normal cell cycle control, primarily to prevent rereplication. Both the checkpoint and replication roles are conserved in human DTL. Our data indicate that the rereplication reflects a requirement for DTL in regulating CDT1, a protein required for prereplication complex formation. CDT1 is degraded in S phase to prevent rereplication, and following DNA damage to prevent origin firing. We show that DTL associates with the CUL4-DDB1 E3 ubiquitin ligase and is required for CDT1 down-regulation in unperturbed cells and following DNA damage. The cell cycle defects of Dtl-deficient zebrafish are suppressed by reducing Cdt1 levels. In contrast, the early G2/M checkpoint defect appears to be Cdt1-independent. Thus, DTL promotes genomic stability through two distinct mechanisms. First, it is an essential component of the CUL4-DDB1 complex that controls CDT1 levels, thereby preventing rereplication. Second, it is required for the early G2/M checkpoint.

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Section: Dtl Associates With the Cul4a-ddb1 E3 Ubiquitin Ligasementioning

confidence: 83%

DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint

Sansam¹,

Shepard²,

Lai³

et al. 2006

Genes Dev.

147

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“…In this report we focused on characterization of a DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein) gene that was previously isolated as one of downregulated genes during retinoic acid-induced differentiation of human embryonal carcinoma cell line, NT2 cells (Cheung et al, 2001) to elucidate its pathophysiologic roles in growth of breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells

et al. 2008

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To investigate the detailed molecular mechanism of mammary carcinogenesis and discover novel therapeutic targets, we previously analysed gene expression profiles of breast cancers. We here report characterization of a significant role of DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein) in mammary carcinogenesis. Semiquantitative RT-PCR and northern blot analyses confirmed upregulation of DTL/RAMP in the majority of breast cancer cases and all of breast cancer cell lines examined. Immunocytochemical and western blot analyses using anti-DTL/RAMP polyclonal antibody revealed cell-cycle-dependent localization of endogenous DTL/RAMP protein in breast cancer cells; nuclear localization was observed in cells at interphase and the protein was concentrated at the contractile ring in cytokinesis process. The expression level of DTL/RAMP protein became highest at G 1 /S phases, whereas its phosphorylation level was enhanced during mitotic phase. Treatment of breast cancer cells, T47D and HBC4, with small-interfering RNAs against DTL/RAMP effectively suppressed its expression and caused accumulation of G 2 /M cells, resulting in growth inhibition of cancer cells. We further demonstrate the in vitro phosphorylation of DTL/ RAMP through an interaction with the mitotic kinase, Aurora kinase-B (AURKB). Interestingly, depletion of AURKB expression with siRNA in breast cancer cells reduced the phosphorylation of DTL/RAMP and decreased the stability of DTL/RAMP protein. These findings imply important roles of DTL/RAMP in growth of breast cancer cells and suggest that DTL/RAMP might be a promising molecular target for treatment of breast cancer.

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“…According to a GenBank BLAST search, nt 700 -811 of S35 showed 86% homology to a region of the human ramp gene, suggesting that S35 is a part of a mouse homologue of ramp (35). The region of nt 1-699 showed no homology with any sequence.…”

Section: Analysis Of Cdna That Coded For the Ag Recognized By At-1 Ctlmentioning

confidence: 99%

Cryptic CTL Epitope on a Murine Sarcoma Meth A Generated by Exon Extension as a Novel Mechanism

Uenaka¹,

Hirano²,

Hata³

et al. 2003

The Journal of Immunology

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Using the recently developed ELISPOT cloning methodology, we obtained cDNA clone S35 coding for the Ag epitope recognized by a murine sarcoma Meth A-specific CTL clone AT-1. Analysis of truncated S35 constructs and overlapping peptides revealed that the peptide epitope was LGAEAIFRL. AT-1 CTL lysed peptide-pulsed CMS8 cells at a nanomolar concentration, and the peptide strongly stimulated IFN-γ production in AT-1 CTL. Sequence homology indicated that the S35 was derived from a mouse homologue of human retinoic acid-regulated nuclear matrix-associated protein (ramp). The ramp gene consisted of 15 exons. The majority of the ramp mRNA was the transcript normally spliced between exons 14 and 15, but a minor population of mRNA with an extended exon 14 was also present in Meth A cells. The epitope was derived from the newly created open reading frame, which resulted from extension of exon 14 after splicing of the adjacent intronic sequence.

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Cloning and Expression of a Novel Nuclear Matrix-associated Protein That Is Regulated during the Retinoic Acid-induced Neuronal Differentiation

Cited by 33 publications

References 40 publications

DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint

DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint

Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells

Cryptic CTL Epitope on a Murine Sarcoma Meth A Generated by Exon Extension as a Novel Mechanism

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