PMID- 10373550
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Jul
TI  - Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic
      AMP-induced transcription for proteolysis.
PG  - 5001-13
AB  - Ubiquitin-mediated proteolysis controls diverse physiological processes in
      eukaryotes. However, few in vivo targets of the mammalian Cdc34 and Rad6
      ubiquitin-conjugating enzymes are known. A yeast-based genetic assay to identify 
      proteins that interact with human Cdc34 resulted in three cDNAs encoding bZIP DNA
      binding motifs. Two of these interactants are repressors of cyclic AMP
      (cAMP)-induced transcription: hICERIIgamma, a product of the CREM gene, and
      hATF5, a novel ATF homolog. Transfection assays with mammalian cells demonstrate 
      both hCdc34- and hRad6B-dependent ubiquitin-mediated proteolysis of hICERIIgamma 
      and hATF5. This degradation requires an active ubiquitin-conjugating enzyme and
      results in abrogation of ICERIIgamma- and ATF5-mediated repression of
      cAMP-induced transcription. Consistent with these results, the endogenous ICER
      protein is elevated in cells which are null for murine Rad6B (mHR6B-/-) or
      transfected with dominant negative and antisense constructs of human CDC34. Based
      on the requirement for CREM/ICER and Rad6B proteins in spermatogenesis, we
      determined expression of Cdc34, Rad6B, CREM/ICER isoforms, and the
      Skp1-Cullin-F-box ubiquitin protein ligase subunits Cul-1 and Cul-2, which are
      associated with Cdc34 activity during murine testicular development. Cdc34,
      Rad6B, and the Cullin proteins are expressed in a developmentally regulated
      manner, with distinctly different patterns for Cdc34 and the Cullin proteins in
      germ cells. The Cdc34 and Rad6B proteins are significantly elevated in meiotic
      and postmeiotic haploid germ cells when chromatin modifications occur. Thus, the 
      stability of specific mammalian transcription factors is the result of complex
      targeting by multiple ubiquitin-conjugating enzymes and may have an impact on
      cAMP-inducible gene regulation during both meiotic and mitotic cell cycles.
FAU - Pati, D
AU  - Pati D
AD  - Texas Children's Cancer Center, Department of Pediatrics, Baylor College of
      Medicine, Houston, Texas 77030, USA.
FAU - Meistrich, M L
AU  - Meistrich ML
FAU - Plon, S E
AU  - Plon SE
LA  - eng
SI  - GENBANK/AF101388
GR  - R01 HD016843/HD/NICHD NIH HHS/United States
GR  - HD16843/HD/NICHD NIH HHS/United States
GR  - P30-HD27832/HD/NICHD NIH HHS/United States
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  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Activating Transcription Factors)
RN  - 0 (Blood Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Ubiquitins)
RN  - 135844-64-3 (Cyclic AMP Response Element Modulator)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.3.2.23 (CDC34 protein, human)
RN  - EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
RN  - EC 2.3.2.23 (Ubiquitin-Protein Ligase Complexes)
RN  - EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Activating Transcription Factors
MH  - Anaphase-Promoting Complex-Cyclosome
MH  - Animals
MH  - Base Sequence
MH  - Blood Proteins/genetics/*metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP Response Element Modulator
MH  - Cysteine Endopeptidases/metabolism
MH  - DNA, Complementary
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Endopeptidases/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Ligases/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/metabolism
MH  - Proteasome Endopeptidase Complex
MH  - Repressor Proteins/genetics/*metabolism
MH  - Spermatogenesis
MH  - Transcription Factors/genetics/*metabolism
MH  - *Transcription, Genetic
MH  - Ubiquitin-Conjugating Enzymes
MH  - *Ubiquitin-Protein Ligase Complexes
MH  - Ubiquitin-Protein Ligases
MH  - Ubiquitins/metabolism
PMC - PMC84326
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1128/MCB.19.7.5001 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jul;19(7):5001-13. doi: 10.1128/MCB.19.7.5001.