PMID- 10652300
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 5
DP  - 2000 Feb 4
TI  - Degradation of cyclin A does not require its phosphorylation by CDC2 and
      cyclin-dependent kinase 2.
PG  - 3158-67
AB  - Many cyclins are degraded by the ubiquitination/proteasome pathways involving the
      anaphase-promoting complex and SCF complexes. These degradations are frequently
      dependent on phosphorylation by cyclin-dependent kinases (CDKs), providing a
      self-limiting mechanism for CDK activity. Here we present evidence from in vitro 
      and in vivo assay systems that the degradation of human cyclin A can be inhibited
      by kinase-inactive mutants of CDK2 and CDC2. One obvious interpretation of these 
      results is that like other cyclins, CDK-dependent phosphorylation of the cyclin A
      may be involved in cyclin A degradation. Our data indicated that CDK2 can
      phosphorylate cyclin A on Ser-154. Site-directed mutagenesis of Ser-154 abolished
      the phosphorylation by recombinant CDK2 in vitro and the majority of cyclin A
      phosphorylation in the cell. Activation of CDK2 and binding to SKP2 or p27(KIP1) 
      were not affected by the phosphorylation of Ser-154. Surprising, in marked
      contrast to cyclin E, where phosphorylation of Thr-380 by CDK2 is required for
      proteolysis, degradation of cyclin A was not affected by Ser-154 phosphorylation.
      It is likely that the stabilization of cyclin A by the kinase-inactive CDKs was
      mainly due to a cell cycle effect. These data suggest an important difference
      between the regulation of cyclin A and cyclin E.
FAU - Yam, C H
AU  - Yam CH
AD  - Department of Biochemistry, The Hong Kong University of Science and Technology,
      Clear Water Bay, Kowloon, Hong Kong, China.
FAU - Siu, W Y
AU  - Siu WY
FAU - Lau, A
AU  - Lau A
FAU - Poon, R Y
AU  - Poon RY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cyclin A)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - CDC2 Protein Kinase/*metabolism
MH  - *CDC2-CDC28 Kinases
MH  - Cell Cycle
MH  - Cyclin A/*metabolism
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Enzyme Activation
MH  - HeLa Cells
MH  - Humans
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
EDAT- 2000/02/01 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1074/jbc.275.5.3158 [doi]
AID - S0021-9258(18)30889-5 [pii]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 4;275(5):3158-67. doi: 10.1074/jbc.275.5.3158.