PMID- 10428031
OWN - NLM
STAT- MEDLINE
DCOM- 19990813
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 98
IP  - 2
DP  - 1999 Jul 23
TI  - mCRY1 and mCRY2 are essential components of the negative limb of the circadian
      clock feedback loop.
PG  - 193-205
AB  - We determined that two mouse cryptochrome genes, mCry1 and mCry2, act in the
      negative limb of the clock feedback loop. In cell lines, mPER proteins (alone or 
      in combination) have modest effects on their cellular location and ability to
      inhibit CLOCK:BMAL1 -mediated transcription. This suggested cryptochrome
      involvement in the negative limb of the feedback loop. Indeed, mCry1 and mCry2
      RNA levels are reduced in the central and peripheral clocks of Clock/Clock mutant
      mice. mCRY1 and mCRY2 are nuclear proteins that interact with each of the mPER
      proteins, translocate each mPER protein from cytoplasm to nucleus, and are
      rhythmically expressed in the suprachiasmatic circadian clock. Luciferase
      reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E
      box-mediated transcription. The mPER and mCRY proteins appear to inhibit the
      transcriptional complex differentially.
FAU - Kume, K
AU  - Kume K
AD  - Laboratory of Developmental Chronobiology, Pediatric Service, Massachusetts
      General Hospital and Harvard Medical School, Boston 02114, USA.
FAU - Zylka, M J
AU  - Zylka MJ
FAU - Sriram, S
AU  - Sriram S
FAU - Shearman, L P
AU  - Shearman LP
FAU - Weaver, D R
AU  - Weaver DR
FAU - Jin, X
AU  - Jin X
FAU - Maywood, E S
AU  - Maywood ES
FAU - Hastings, M H
AU  - Hastings MH
FAU - Reppert, S M
AU  - Reppert SM
LA  - eng
SI  - GENBANK/AF156987
GR  - MH11547/MH/NIMH NIH HHS/United States
GR  - MH12067/MH/NIMH NIH HHS/United States
GR  - R37 HD14427/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (ARNTL Transcription Factors)
RN  - 0 (ARNTL protein, human)
RN  - 0 (Arntl protein, mouse)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cryptochromes)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Eye Proteins)
RN  - 0 (Flavoproteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PER1 protein, human)
RN  - 0 (PER2 protein, human)
RN  - 0 (Per1 protein, mouse)
RN  - 0 (Per2 protein, mouse)
RN  - 0 (Period Circadian Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (cry protein, Drosophila)
RN  - EC 2.3.1.48 (CLOCK Proteins)
RN  - EC 2.3.1.48 (CLOCK protein, human)
RN  - EC 2.3.1.48 (Clock protein, mouse)
SB  - IM
MH  - 3T3 Cells
MH  - ARNTL Transcription Factors
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Biological Clocks/*physiology
MH  - Blotting, Western
MH  - CLOCK Proteins
MH  - COS Cells
MH  - Cell Cycle Proteins
MH  - Cell Nucleus/metabolism
MH  - Cloning, Molecular
MH  - Cryptochromes
MH  - *Drosophila Proteins
MH  - *Eye Proteins
MH  - Feedback/physiology
MH  - Female
MH  - Flavoproteins/analysis/*genetics/metabolism
MH  - Gene Expression/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/metabolism
MH  - Period Circadian Proteins
MH  - *Photoreceptor Cells, Invertebrate
MH  - RNA, Messenger/metabolism
MH  - Receptors, G-Protein-Coupled
MH  - Suprachiasmatic Nucleus/chemistry/metabolism
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic/physiology
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - S0092-8674(00)81014-4 [pii]
AID - 10.1016/s0092-8674(00)81014-4 [doi]
PST - ppublish
SO  - Cell. 1999 Jul 23;98(2):193-205. doi: 10.1016/s0092-8674(00)81014-4.