24-Hour oscillation of mouse methionine aminopeptidase2, a regulator of tumor progression, is regulated by clock gene proteins

Hiroo Nakagawa, Koyanagi Satoru, Takako Takiguchi, Yukako Kuramoto, Shinji Soeda, Hiroshi Shimeno, Shun Higuchi, Shigehiro Ohdo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Methionine aminopeptidase2 (MetAP2) plays an important role in the growth of endothelial cells during the tumor angiogenesis stage. Recently, we have clarified that mouse methionine aminopeptidases (mMetAPs) show a 24-hour rhythm in implanted tumor masses. In the present study, we investigated the mechanism underlying the 24-hour rhythm of mMetAP2 activity in tumor-bearing mice under a light-dark (lights on from 7 a.m. to 7 p.m.) cycle. The 5′ flanking region of mMetAP2 included eight E-boxes. The transcription of the mMetAP2 promoter was enhanced by the mCLOCK:mBMAL1 heterodimer, and its activation was inhibited by mPER2 or mCRY1. Deletion and mutation of the E-boxes in the region indicated that the E-box nearest to the initiation start site played an important role in the transcriptional regulation by clock genes. In sarcoma180-bearing mice, the pattern of binding of mCLOCK and mBMAL1 to the E-box and transcription of the mMetAP2 promoter showed a 24-hour rhythm with higher levels from the mid-light to early dark phase. The pattern of mMetAP2 transcription was closely associated with that of mMetAP2 mRNA expression in three types of tumor-bearing mice. mMetAP2 protein expression varied with higher levels from the late-dark to early light phase. The rhythmicity of the protein expression was synchronous with that of the activity of mMetAPs but out of phase with that of the mMetAP2 mRNA expression. These results suggest that the 24-hour rhythm of mMetAP2 activity is regulated by the transcription of clock genes within the clock feedback loops.

Original languageEnglish
Pages (from-to)8328-8333
Number of pages6
JournalCancer Research
Volume64
Issue number22
DOIs
Publication statusPublished - Nov 15 2004

Fingerprint

Methionine
Light
Aminopeptidases
Neoplasms
Proteins
Messenger RNA
Sequence Deletion
5' Flanking Region
Periodicity
Genes
Endothelial Cells
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

24-Hour oscillation of mouse methionine aminopeptidase2, a regulator of tumor progression, is regulated by clock gene proteins. / Nakagawa, Hiroo; Satoru, Koyanagi; Takiguchi, Takako; Kuramoto, Yukako; Soeda, Shinji; Shimeno, Hiroshi; Higuchi, Shun; Ohdo, Shigehiro.

In: Cancer Research, Vol. 64, No. 22, 15.11.2004, p. 8328-8333.

Research output: Contribution to journalArticle

Nakagawa, Hiroo ; Satoru, Koyanagi ; Takiguchi, Takako ; Kuramoto, Yukako ; Soeda, Shinji ; Shimeno, Hiroshi ; Higuchi, Shun ; Ohdo, Shigehiro. / 24-Hour oscillation of mouse methionine aminopeptidase2, a regulator of tumor progression, is regulated by clock gene proteins. In: Cancer Research. 2004 ; Vol. 64, No. 22. pp. 8328-8333.
@article{d29fd803d4e8424ea03475f60b6f799a,
title = "24-Hour oscillation of mouse methionine aminopeptidase2, a regulator of tumor progression, is regulated by clock gene proteins",
abstract = "Methionine aminopeptidase2 (MetAP2) plays an important role in the growth of endothelial cells during the tumor angiogenesis stage. Recently, we have clarified that mouse methionine aminopeptidases (mMetAPs) show a 24-hour rhythm in implanted tumor masses. In the present study, we investigated the mechanism underlying the 24-hour rhythm of mMetAP2 activity in tumor-bearing mice under a light-dark (lights on from 7 a.m. to 7 p.m.) cycle. The 5′ flanking region of mMetAP2 included eight E-boxes. The transcription of the mMetAP2 promoter was enhanced by the mCLOCK:mBMAL1 heterodimer, and its activation was inhibited by mPER2 or mCRY1. Deletion and mutation of the E-boxes in the region indicated that the E-box nearest to the initiation start site played an important role in the transcriptional regulation by clock genes. In sarcoma180-bearing mice, the pattern of binding of mCLOCK and mBMAL1 to the E-box and transcription of the mMetAP2 promoter showed a 24-hour rhythm with higher levels from the mid-light to early dark phase. The pattern of mMetAP2 transcription was closely associated with that of mMetAP2 mRNA expression in three types of tumor-bearing mice. mMetAP2 protein expression varied with higher levels from the late-dark to early light phase. The rhythmicity of the protein expression was synchronous with that of the activity of mMetAPs but out of phase with that of the mMetAP2 mRNA expression. These results suggest that the 24-hour rhythm of mMetAP2 activity is regulated by the transcription of clock genes within the clock feedback loops.",
author = "Hiroo Nakagawa and Koyanagi Satoru and Takako Takiguchi and Yukako Kuramoto and Shinji Soeda and Hiroshi Shimeno and Shun Higuchi and Shigehiro Ohdo",
year = "2004",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-04-2122",
language = "English",
volume = "64",
pages = "8328--8333",
journal = "Cancer Research",
issn = "0008-5472",
number = "22",

}

TY - JOUR

T1 - 24-Hour oscillation of mouse methionine aminopeptidase2, a regulator of tumor progression, is regulated by clock gene proteins

AU - Nakagawa, Hiroo

AU - Satoru, Koyanagi

AU - Takiguchi, Takako

AU - Kuramoto, Yukako

AU - Soeda, Shinji

AU - Shimeno, Hiroshi

AU - Higuchi, Shun

AU - Ohdo, Shigehiro

PY - 2004/11/15

Y1 - 2004/11/15

N2 - Methionine aminopeptidase2 (MetAP2) plays an important role in the growth of endothelial cells during the tumor angiogenesis stage. Recently, we have clarified that mouse methionine aminopeptidases (mMetAPs) show a 24-hour rhythm in implanted tumor masses. In the present study, we investigated the mechanism underlying the 24-hour rhythm of mMetAP2 activity in tumor-bearing mice under a light-dark (lights on from 7 a.m. to 7 p.m.) cycle. The 5′ flanking region of mMetAP2 included eight E-boxes. The transcription of the mMetAP2 promoter was enhanced by the mCLOCK:mBMAL1 heterodimer, and its activation was inhibited by mPER2 or mCRY1. Deletion and mutation of the E-boxes in the region indicated that the E-box nearest to the initiation start site played an important role in the transcriptional regulation by clock genes. In sarcoma180-bearing mice, the pattern of binding of mCLOCK and mBMAL1 to the E-box and transcription of the mMetAP2 promoter showed a 24-hour rhythm with higher levels from the mid-light to early dark phase. The pattern of mMetAP2 transcription was closely associated with that of mMetAP2 mRNA expression in three types of tumor-bearing mice. mMetAP2 protein expression varied with higher levels from the late-dark to early light phase. The rhythmicity of the protein expression was synchronous with that of the activity of mMetAPs but out of phase with that of the mMetAP2 mRNA expression. These results suggest that the 24-hour rhythm of mMetAP2 activity is regulated by the transcription of clock genes within the clock feedback loops.

AB - Methionine aminopeptidase2 (MetAP2) plays an important role in the growth of endothelial cells during the tumor angiogenesis stage. Recently, we have clarified that mouse methionine aminopeptidases (mMetAPs) show a 24-hour rhythm in implanted tumor masses. In the present study, we investigated the mechanism underlying the 24-hour rhythm of mMetAP2 activity in tumor-bearing mice under a light-dark (lights on from 7 a.m. to 7 p.m.) cycle. The 5′ flanking region of mMetAP2 included eight E-boxes. The transcription of the mMetAP2 promoter was enhanced by the mCLOCK:mBMAL1 heterodimer, and its activation was inhibited by mPER2 or mCRY1. Deletion and mutation of the E-boxes in the region indicated that the E-box nearest to the initiation start site played an important role in the transcriptional regulation by clock genes. In sarcoma180-bearing mice, the pattern of binding of mCLOCK and mBMAL1 to the E-box and transcription of the mMetAP2 promoter showed a 24-hour rhythm with higher levels from the mid-light to early dark phase. The pattern of mMetAP2 transcription was closely associated with that of mMetAP2 mRNA expression in three types of tumor-bearing mice. mMetAP2 protein expression varied with higher levels from the late-dark to early light phase. The rhythmicity of the protein expression was synchronous with that of the activity of mMetAPs but out of phase with that of the mMetAP2 mRNA expression. These results suggest that the 24-hour rhythm of mMetAP2 activity is regulated by the transcription of clock genes within the clock feedback loops.

UR - http://www.scopus.com/inward/record.url?scp=8544275870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8544275870&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-2122

DO - 10.1158/0008-5472.CAN-04-2122

M3 - Article

C2 - 15548701

AN - SCOPUS:8544275870

VL - 64

SP - 8328

EP - 8333

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 22

ER -