The ubiquitin ligase CHIP regulates c-Myc stability and transcriptional activity

摘要: c-Myc is a proto-oncogenic transcription factor and its rapid turnover mediated by the ubiquitin-proteasome system critical for maintaining normal cellular homeostasis. Multiple ubiquitin ligases have been assigned regulation till date. However, available data suggest possible existence of additional E3 ligase(s). Here, we report new ligase c-Myc, carboxyl terminus Hsc70-interacting protein or CHIP, which chaperone-associated Ubox-containing ligase. In this report, show that CHIP interacts ubiquitinates thus targeting it proteasome-mediated degradation. Overexpression could accelerate rate protein. Conversely, knockdown RNAi stabilizes endogenous c-Myc. The interaction between depends on N-terminally located tetratricopeptide repeats has implicated as chaperone-binding motif. Inhibition Hsp90 chaperone activity 17-N-allylamino-17-demethoxygeldanamycin reduces level. We found association dependent chaperones; particularly Hsp70. antagonizes transcriptional decreases abundance transcripts target genes. Overall, CHIP-knockdown increases malignant behavior C6 glioma cells. To best our knowledge, first being regulated bona-fide in HEK293 well Because reported earlier to be negatively regulating Akt1, BCR-ABL hTERT, now present study may strengthen view acts tumor suppressor.