PMID- 10481010
OWN - NLM
STAT- MEDLINE
DCOM- 19991008
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 285
IP  - 5434
DP  - 1999 Sep 10
TI  - A role for the proteasome in the light response of the timeless clock protein.
PG  - 1737-41
AB  - The cyclic expression of the period (PER) and timeless (TIM) proteins is critical
      for the molecular circadian feedback loop in Drosophila. The entrainment by light
      of the circadian clock is mediated by a reduction in TIM levels. To elucidate the
      mechanism of this process, the sensitivity of TIM regulation by light was tested 
      in an in vitro assay with inhibitors of candidate proteolytic pathways. The data 
      suggested that TIM is degraded through a ubiquitin-proteasome mechanism. In
      addition, in cultures from third-instar larvae, TIM degradation was blocked
      specifically by inhibitors of proteasome activity. Degradation appeared to be
      preceded by tyrosine phosphorylation. Finally, TIM was ubiquitinated in response 
      to light in cultured cells.
FAU - Naidoo, N
AU  - Naidoo N
AD  - Howard Hughes Medical Institute, Department of Neuroscience, University of
      Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
FAU - Song, W
AU  - Song W
FAU - Hunter-Ensor, M
AU  - Hunter-Ensor M
FAU - Sehgal, A
AU  - Sehgal A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Insect Proteins)
RN  - 0 (Leupeptins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Ubiquitins)
RN  - 0 (carbobenzoxy-leucyl-leucyl-norvalinal)
RN  - 0 (tim protein, Drosophila)
RN  - 133343-34-7 (lactacystin)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - GMW67QNF9C (Leucine)
RN  - I0J33N5627 (ubenimex)
RN  - J97339NR3V (leupeptin)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/analogs & derivatives/pharmacology
MH  - Animals
MH  - *Biological Clocks
MH  - Cells, Cultured
MH  - *Circadian Rhythm
MH  - Cysteine Endopeptidases/*physiology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Darkness
MH  - Drosophila
MH  - *Drosophila Proteins
MH  - Feedback
MH  - Insect Proteins/*metabolism
MH  - Leucine/analogs & derivatives/pharmacology
MH  - Leupeptins/pharmacology
MH  - *Light
MH  - Multienzyme Complexes/*physiology
MH  - Neurons/*metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine/metabolism
MH  - Protease Inhibitors/pharmacology
MH  - Proteasome Endopeptidase Complex
MH  - Ubiquitins/metabolism
EDAT- 1999/09/11 00:00
MHDA- 1999/09/11 00:01
CRDT- 1999/09/11 00:00
PHST- 1999/09/11 00:00 [pubmed]
PHST- 1999/09/11 00:01 [medline]
PHST- 1999/09/11 00:00 [entrez]
AID - 7807 [pii]
AID - 10.1126/science.285.5434.1737 [doi]
PST - ppublish
SO  - Science. 1999 Sep 10;285(5434):1737-41. doi: 10.1126/science.285.5434.1737.