Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut

Neufeld, Ellis J.; Skalnik, David G.; Lievens, Patricia; Orkin, Stuart H.

doi:10.1038/ng0492-50

Cited by 205 publications

(221 citation statements)

References 31 publications

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“…Nuclear extracts from selected samples of pairs of uterine leiomyomas and matched normal myometrium were prepared as described in Material and Methods and analyzed by EMSA with oligonucleotides containing a CDP/Cut consensus-binding site (CGATATCGAT). DNA and proteins were incubated either with no antibody (lanes 1-10) or with the indicated antibodies (lanes [11][12][13][14]. The diagram shows a schematic representation of the CDP/Cux proteins with their conserved domains and the regions recognized by the respective antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…However, this notion contradicts results of DNA binding studies in tissue culture systems. CUTL1 encodes for the CDP/Cux protein, which was characterized independently as the CDP and the DNA binding subunit of the HiNF-D. [12][13][14] The DNA binding activity of HiNF-D was upregulated in S phase in normal cells but constitutively activated in tumor cell lines. [15][16][17][18] CDP/Cux is a transcription factor that contains 4 DNA binding domains and whose expression has been associated with cellular proliferation, the repression of genes that are turned on in terminally differentiated cells and the regulation of MARs.…”

mentioning

confidence: 99%

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Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

Moon

Zeng

Premdas

et al. 2002

Intl Journal of Cancer

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Genetic analyses and mRNA expression studies have implicated CUTL1 as a candidate tumor-suppressor gene in uterine leiomyomas and breast cancers. However, modulation of CDP/Cux, the protein encoded by CUTL1, does not agree with this notion. The activity of CDP/Cux, which is the DNA binding subunit of HiNF-D, was upregulated as normal cells progressed into S phase and constitutively elevated in several tumor cell lines. Activation of CDP/Cux at the G 1 /S transition involved the proteolytic processing of the protein to generate a shorter isoform. Uterine leiomyomas represent a unique reagent for molecular analysis because they are resected as homogenous tumor tissue together with the adjacent normal myometrium and they are often very large. In the present study, proteins were isolated from 16 pairs of matched tumors and adjacent myometrium and analyzed by Western blot and electrophoretic mobility shift assays. Strikingly, in 11/16 tumors, the steady-state level of small CDP/ Cux isoforms was increased compared to normal control tissue. Where tested, a corresponding increase in CDP/Cux stable DNA binding activity was observed. DNA sequencing analysis of CUTL1 cDNAs from 6 leiomyomas, including 4 with LOH of CUTL1, did not reveal any gross rearrangement or point mutations. Altogether these findings suggest that CUTL1 is probably not the tumor suppressor on 7q22. Moreover, the frequent increase in smaller CDP/Cux isoforms indicates that molecular events associated with the truncation of CDP/Cux proteins may be selected in uterine leiomyomas.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

Moon

Zeng

Premdas

et al. 2002

Intl Journal of Cancer

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“…Multiple CUX1 isoforms have been described, two of which are ubiquitously expressed 2,22,[24][25][26][27] (reviewed in REF. 28).…”

Section: Molecular and Cellular Functions Of Cux1mentioning

confidence: 99%

“…to as p200 CUX1, contains four evolutionarily conserved DNA-binding domains: that is, three CUT repeats (CR1, CR2 and CR3) and a CUT homeodomain (HD) 2 . On the basis of reporter assays and in vitro DNA binding assays, early studies described p200 CUX1 as a transcriptional repressor that functions in myeloid precursor cells to downregulate the expression of genes that become expressed only in terminally differentiated cells [29][30][31][32][33] .…”

Section: Non-oncogene Addictionsmentioning

confidence: 99%

“…These properties are not consistent with a role as a classical transcription factor that stably binds to DNA and recruits a co-activator or a co-repressor, but it is still possible for this protein to repress transcription by competition for occupancy of the binding site 37 . Indeed, as mentioned above, CUX1 was originally purified as CDP 2,29 . In addition to its presumed role in transcriptional repression, it was recently shown that p200 CUX1 has a direct role in DNA repair through its three CUT repeat domains 18 .…”

Section: Non-oncogene Addictionsmentioning

confidence: 99%

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CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

Ramdzan

Nepveu

2014

Nat Rev Cancer

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Cell cycle-dependent modifications in activities of pRb-related tumor suppressors and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells

et al. 1997

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The histone H4 gene promoter provides a paradigm for defining transcriptional control operative at the G1/S phase transition point in the cell cycle. Transcription of the cell cycle-dependent histone H4 gene is upregulated at the onset of S phase, and the cell cycle control element that mediates this activation has been functionally mapped to a proximal promoter domain designated Site II. Activity of Site II is regulated by an E2F-independent mechanism involving binding of the oncoprotein IRF2 and the multisubunit protein HiNF-D, which contains the homeodomain CDP/cut, CDC2, cyclin A, and the tumor suppressor pRb. To address mechanisms that define interactions of Site II regulatory factors with this cell cycle control element, we have investigated these determinants of transcriptional regulation at the G1/S phase transition in FDC-P1 hematopoietic progenitor cells. The representation and activities of histone gene regulatory factors were examined as a function of FDC-P1 growth stimulation. We find striking differences in expression of the pRb-related growth regulatory proteins (pRb/p105, pRb2/p130, and p107) following the onset of proliferation. pRb2/p130 is present at elevated levels in quiescent cells and declines following growth stimulation. By contrast, pRb and p107 are minimally represented in quiescent FDC-P1 cells but are upregulated at the G1/S phase transition point. We also observe a dramatic upregulation of the cellular levels of pRb2/p130-associated protein kinase activity when S phase is initiated. Selective interactions of pRb and p107 with CDP/cut are observed during the FDC-P1 cell cycle and suggest functional linkage to competency for DNA binding and/or transcriptional activity. These results are particularly significant in the context of hematopoietic differentiation where stringent control of the cell cycle program is requisite for expanding the stem cell population during development and tissue renewal.

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Human CCAAT displacement protein is homologous to the Drosophila homeoprotein, cut

Cited by 205 publications

References 31 publications

Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

Expression of N‐terminally truncated isoforms of CDP/CUX is increased in human uterine leiomyomas

CUX1, a haploinsufficient tumour suppressor gene overexpressed in advanced cancers

Cell cycle-dependent modifications in activities of pRb-related tumor suppressors and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells

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