Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells

Elena Sancho, Maya R. Vilá, Luis Sánchez-Pulido, Juan José Lozano, Rosanna Paciucci, Marga Nadal, Margaret Fox, Clare Harvey, Brenda Bercovich, Nourredine Loukili, Aaron Ciechanover, Stanley L. Lin, Ferran Sanz, Xavier P. Estivill, Alfonso Valencia, Timothy M. Thomson

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

By means of differential RNA display, we have isolated a cDNA corresponding to transcripts that are down-regulated upon differentiation of the goblet cell-like HT-29-M6 human colon carcinoma cell line. These transcripts encode proteins originally identified as CROC-1 on the basis of their capacity to activate transcription of c-fos. We show that these proteins are similar in sequence, and in predicted secondary and tertiary structure, to the ubiquitin-conjugating enzymes, also known as E2. Despite the similarities, these proteins lack a critical cysteine residue essential for the catalytic activity of E2 enzymes and, in vitro, they do not conjugate or transfer ubiquitin to protein substrates. These proteins constitute a distinct subfamily within the E2 protein family and are highly conserved in phylogeny from yeasts to mammals. Therefore, we have designated them UEV (ubiquitin-conjugating E2 enzyme variant) proteins, defined as proteins similar in sequence and structure to the E2 ubiquitin-conjugating enzymes but lacking their enzymatic activity (HW/GDB-approved gene symbol, UBE2V). At least two human genes code for UEV Proteins, and one of them, located on chromosome 20q13.2, is expressed as at least four isoforms, generated by alternative splicing. All human cell types analyzed expressed at least one of these isoforms. Constitutive expression of exogenous human UEV in HT-29-M6 cells inhibited their capacity to differentiate upon confluence and caused both the entry of a larger proportion of cells in the division cycle and an accumulation in G2-M. This was accompanied with a profound inhibition of the mitotic kinase, cdk1. These results suggest that UEV proteins are involved in the control of differentiation and could exert their effects by altering cell cycle distribution.

Original languageEnglish
Pages (from-to)576-589
Number of pages14
JournalMolecular and Cellular Biology
Volume18
Issue number1
Publication statusPublished - Jan 1998
Externally publishedYes

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Ubiquitin-Conjugating Enzymes
Cell Cycle
Proteins
Ubiquitin
Protein Isoforms
In Vitro Techniques
CDC2 Protein Kinase
HT29 Cells
Goblet Cells
Alternative Splicing
Phylogeny
Genes
Cysteine
Mammals
Colon
Complementary DNA
Chromosomes
Yeasts

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sancho, E., Vilá, M. R., Sánchez-Pulido, L., Lozano, J. J., Paciucci, R., Nadal, M., ... Thomson, T. M. (1998). Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Molecular and Cellular Biology, 18(1), 576-589.

Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. / Sancho, Elena; Vilá, Maya R.; Sánchez-Pulido, Luis; Lozano, Juan José; Paciucci, Rosanna; Nadal, Marga; Fox, Margaret; Harvey, Clare; Bercovich, Brenda; Loukili, Nourredine; Ciechanover, Aaron; Lin, Stanley L.; Sanz, Ferran; Estivill, Xavier P.; Valencia, Alfonso; Thomson, Timothy M.

In: Molecular and Cellular Biology, Vol. 18, No. 1, 01.1998, p. 576-589.

Research output: Contribution to journalArticle

Sancho, E, Vilá, MR, Sánchez-Pulido, L, Lozano, JJ, Paciucci, R, Nadal, M, Fox, M, Harvey, C, Bercovich, B, Loukili, N, Ciechanover, A, Lin, SL, Sanz, F, Estivill, XP, Valencia, A & Thomson, TM 1998, 'Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells', Molecular and Cellular Biology, vol. 18, no. 1, pp. 576-589.
Sancho, Elena ; Vilá, Maya R. ; Sánchez-Pulido, Luis ; Lozano, Juan José ; Paciucci, Rosanna ; Nadal, Marga ; Fox, Margaret ; Harvey, Clare ; Bercovich, Brenda ; Loukili, Nourredine ; Ciechanover, Aaron ; Lin, Stanley L. ; Sanz, Ferran ; Estivill, Xavier P. ; Valencia, Alfonso ; Thomson, Timothy M. / Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. In: Molecular and Cellular Biology. 1998 ; Vol. 18, No. 1. pp. 576-589.
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abstract = "By means of differential RNA display, we have isolated a cDNA corresponding to transcripts that are down-regulated upon differentiation of the goblet cell-like HT-29-M6 human colon carcinoma cell line. These transcripts encode proteins originally identified as CROC-1 on the basis of their capacity to activate transcription of c-fos. We show that these proteins are similar in sequence, and in predicted secondary and tertiary structure, to the ubiquitin-conjugating enzymes, also known as E2. Despite the similarities, these proteins lack a critical cysteine residue essential for the catalytic activity of E2 enzymes and, in vitro, they do not conjugate or transfer ubiquitin to protein substrates. These proteins constitute a distinct subfamily within the E2 protein family and are highly conserved in phylogeny from yeasts to mammals. Therefore, we have designated them UEV (ubiquitin-conjugating E2 enzyme variant) proteins, defined as proteins similar in sequence and structure to the E2 ubiquitin-conjugating enzymes but lacking their enzymatic activity (HW/GDB-approved gene symbol, UBE2V). At least two human genes code for UEV Proteins, and one of them, located on chromosome 20q13.2, is expressed as at least four isoforms, generated by alternative splicing. All human cell types analyzed expressed at least one of these isoforms. Constitutive expression of exogenous human UEV in HT-29-M6 cells inhibited their capacity to differentiate upon confluence and caused both the entry of a larger proportion of cells in the division cycle and an accumulation in G2-M. This was accompanied with a profound inhibition of the mitotic kinase, cdk1. These results suggest that UEV proteins are involved in the control of differentiation and could exert their effects by altering cell cycle distribution.",
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AU - Lozano, Juan José

AU - Paciucci, Rosanna

AU - Nadal, Marga

AU - Fox, Margaret

AU - Harvey, Clare

AU - Bercovich, Brenda

AU - Loukili, Nourredine

AU - Ciechanover, Aaron

AU - Lin, Stanley L.

AU - Sanz, Ferran

AU - Estivill, Xavier P.

AU - Valencia, Alfonso

AU - Thomson, Timothy M.

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