Androgen regulation of the human FERM domain encoding gene EHM2 in a cell model of steroid-induced differentiation.
We have developed a cell model to investigate steroid control of differentiation using a subline of HT1080 cells (HT-AR1) that have been engineered to express the human androgen receptor. Dihydrotestosterone (DHT) treatment of HT-AR1 cells induced growth arrest and cytoskeletal reorganization that was associated with the expression of fibronectin and the neuroendocrine markers chromogranin A and neuron-specific enolase. Expression profiling analysis identified the human FERM domain-encoding gene EHM2 as uniquely induced in HT-AR1 cells as compared to 16 other FERM domain containing genes. Since FERM domain proteins control cytoskeletal functions in differentiating cells, and the human EHM2 gene has not been characterized, we investigated EHM2 steroid-regulation, genomic organization, and sequence conservation. We found that DHT, but not dexamethasone, induced the expression of a 3.8 kb transcript in HT-AR1 cells encoding a 504 amino acid protein, and moreover, that human brain tissue contains a 5.8 kb transcript encoding a 913 amino acid isoform. Construction of an unrooted phylogenetic tree using 98 FERM domain proteins revealed that the human EHM2 gene is a member of a distinct subfamily consisting of nine members, all of which contain a highly conserved 325 amino acid FERM domain.
Chauhan
Sanjay
S
Department of Biochemistry and Molecular Biophysics, University of Arizona, Tucson, AZ 85721, USA.
Pandey
Ritu
R
Way
Jeffrey F
JF
Sroka
Thomas C
TC
Demetriou
Manolis C
MC
Kunz
Susan
S
Cress
Anne E
AE
Mount
David W
DW
Miesfeld
Roger L
RL
D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D013196:Dihydrotestosterone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000145:classification; D008969:Molecular Sequence Data; D009479:Neuropeptides; D009490:Neurosecretory Systems / Q000166:cytology; D010641:Phenotype; D010802:Phylogeny; D014176:Protein Biosynthesis; D015202:Protein Engineering; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic
D000728:Androgens; D003598:Cytoskeletal Proteins; C478965:EPB41L4B protein, human; D008565:Membrane Proteins; D009479:Neuropeptides; D011506:Proteins; D011944:Receptors, Androgen; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D013196:Dihydrotestosterone