Hsf-1 and POB1 induce drug sensitivity and apoptosis by inhibiting Ralbp1.
Hsf-1 (heat shock factor-1) is a transcription factor that is known to regulate cellular heat shock response through its binding with the multispecific transporter protein, Ralbp1. Results of present studies demonstrate that Hsf-1 causes specific and saturable inhibition of the transport activity of Ralbp1 and that the combination of Hsf-1 and POB1 causes nearly complete inhibition through specific bindings with Ralbp1. Augmentation of cellular levels of Hsf-1 and POB1 caused dramatic apoptosis in non-small cell lung cancer cell line H358 through Ralbp1 inhibition. These findings indicate a novel model for mutual regulation of Hsf-1 and Ralbp1 through Ralbp1-mediated sequestration of Hsf-1 in the cellular cytoskeleton and Hsf-1-mediated inhibition of the transport activity of membrane-bound Ralbp1.
Singhal
Sharad S
SS
Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, Texas 76107-2699, USA.
Yadav
Sushma
S
Drake
Kenneth
K
Singhal
Jyotsana
J
Awasthi
Sanjay
S
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D002135:Calcium-Binding Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020014:K562 Cells; D008175:Lung Neoplasms / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D000076249:Heat Shock Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; C095637:RALBP1 protein, human; C489722:REPS2 protein, human; D014157:Transcription Factors