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: UMLS:C0598934 (
tumor growth
)
58,965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The transcription factor c-Myc and two cullin family members CUL4A/4B function as oncogenes in colorectal cancer. Our recent publication reveals that c-Myc specifically activates the expression of
CUL4A/4B
through binding to their promoters. However, the underlying mechanism of how c-Myc actions in this process is still unknown. Using mass spectrometry and immunoprecipitation assays, we identified c-Myc formed a transcriptional complex with its partner Max (
Myc-associated factor X
), a histone acetyltransferase p300 and a coactivator associated arginine methyltransferase 1 (CARM1) in the present study. Knockdown or overexpression of the components of CARM1-p300-c-Myc-Max (CPCM) complex resulted in a decrease or increase of
CUL4A/4B
levels, respectively. Individual knockdown or inhibition of CPCM components decreased cell proliferation, colony formation, and cell invasion. Biochemically, knockdown or inhibition of CPCM components decreased their occupancies on the promoters of
CUL4A
/
4B
and resulted in their downregulation. Importantly, inhibition of CPCM components also caused a decrease of CRL4 E3 ligase activities and eventually led to an accumulation of ST7 (suppression of tumorigenicity 7), the specific substrate of CRL4 E3 ligases in colorectal cancer. Moreover, the
in vivo
tumor formation results indicated that knockdown or inhibition of CPCM components significantly decreased the tumor volumes. Together, our results suggest that the CPCM complex mediates explicitly the expression of
CUL4A/4B
, and thus affects the stability of CRL4 E3 ligases and the ubiquitination of ST7. These results provide more options by targeting the CPCM components to inhibit
tumor growth
in the therapy of colorectal cancer.
...
PMID:The CARM1-p300-c-Myc-Max (CPCM) transcriptional complex regulates the expression of
CUL4A/4B
and affects the stability of CRL4 E3 ligases in colorectal cancer. 3214 74
