Molecule Information

General Information of the Molecule (ID: Mol00488)

Name	Max dimerization protein 4 (MXD4) ,Homo sapiens
Synonyms	Max dimerizer 4; Class C basic helix-loop-helix protein 12; bHLHc12; Max-associated protein 4; Max-interacting transcriptional repressor MAD4; BHLHC12; MAD4 Click to Show/Hide
Molecule Type	Protein
Gene Name	MXD4
Gene ID	10608
Location	chr4:2247432-2262109[-]
Sequence	MELNSLLILLEAAEYLERRDREAEHGYASVLPFDGDFAREKTKAAGLVRKAPNNRSSHNE LEKHRRAKLRLYLEQLKQLVPLGPDSTRHTTLSLLKRAKVHIKKLEEQDRRALSIKEQLQ QEHRFLKRRLEQLSVQSVERVRTDSTGSAVSTDDSEQEVDIEGMEFGPGELDSVGSSSDA DDHYSLQSGTGGDSGFGPHCRRLGRPALS Click to Show/Hide
Function	Transcriptional repressor. Binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. Antagonizes MYC transcriptional activity by competing for MAX and suppresses MYC dependent cell transformation (By similarity). Click to Show/Hide
Uniprot ID	MAD4_HUMAN
Ensembl ID	ENSG00000123933
HGNC ID	HGNC:13906
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

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Bortezomib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Disease Class: Cutaneous T-cell lymphomas				[1]
Resistant Disease	Cutaneous T-cell lymphomas [ICD-11: 2B00.0]			Disease Info
Resistant Drug	Bortezomib			Drug Info
Molecule Alteration	Expression		Down-regulation
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	MyLa2000 cells	Skin	Homo sapiens (Human)	CVCL_8328
	SeAx cells	Skin	Homo sapiens (Human)	CVCL_5363
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Bortezomib repressed cMyc and simultaneously induced miR-125b-5p that exerted a cytoprotective effect through the downmodulation of MAD4. miR-125b-5p can regulates tumor growth in vivo,and increases cellular resistance to proteasome inhibitors via modulation of MAD4.

References

Ref 1	cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas. PLoS One. 2013;8(3):e59390. doi: 10.1371/journal.pone.0059390. Epub 2013 Mar 19.