Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.22.54 (
calpain 3
)
430
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In this report, we present novel findings that implicate CCAAT/enhancer-binding protein (C/EBPalpha) in regulating the expression and activity of
calpain 3
in vivo and data showing a new physiological substrate for
calpain 3
,
cyclin A
. Our results demonstrate that cleavage of
cyclin A
by
calpain 3
occurs in mouse and human myeloid precursor cells. Calpain 3 cleaves
cyclin A
in vitro and in vivo, resulting in the production of a truncated product that lacks the N-terminal destruction box required for its degradation at the end of mitosis. The cleaved form of
cyclin A
retains the cyclin-dependent kinase (cdk) binding domain and forms active complexes with cdk2. Calpain 3-mediated cleavage of
cyclin A
is lacking in C/EBPalpha-/- mice, which are not able to produce mature granulocytes. Our data support a model in which
calpain 3
-mediated cleavage of
cyclin A
in dividing myeloid progenitor cells is important for the onset of differentiation. Deficits in this pathway in C/EBPalpha-/- mice might contribute to the failure of these mice to produce mature granulocytes. These data reveal a new pathway involving tightly controlled post-translational processing of
cyclin A
during differentiation of granulocytes.
...
PMID:C/EBPalpha is required for proteolytic cleavage of cyclin A by calpain 3 in myeloid precursor cells. 1210 98
