Functional role of KLF10 in multiple disease processes.
Since the discovery by this laboratory of the zinc finger transcription factor, KLF10, a member of the Krüppel-like family of transcription factors, there have been multiple publications regarding its functions and its immediate family members, in numerous cell types. KLF10 has been shown to be rapidly induced by TGFbeta1, 2, 3, E(2), epidermal growth factor, and bone morphogenetic protein-2. TGFbeta inducible early gene-1 activates the TGFbeta-Smad signaling pathway via repression of Smad 7 expression and activation of Smad 2 expression and activity. Overall, KLF10 has been implicated in cell differentiation, as a target gene for a variety of signaling pathways, and in serving as a potential marker for human diseases such as breast cancer, cardiac hypertrophy, and osteoporosis. Like other KLF members, KLF10 is expressed in specific cell types in numerous tissues and is known to be involved in repressing cell proliferation and inflammation as well as inducing apoptosis similar to that of TGFbeta. KLF10 binds to Sp-1-GC rich DNA sequences and can activate or repress the transcription of a number of genes. Overall, KLF10 has been shown to play a major role in the TGFbeta inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGFbeta.
Subramaniam
Malayannan
M
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. subramaniam.malayannan@mayo.edu
Hawse
John R
JR
Rajamannan
Nalini M
NM
Ingle
James N
JN
Spelsberg
Thomas C
TC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000503:physiopathology; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000502:physiology; D001943:Breast Neoplasms / Q000503:physiopathology; D006332:Cardiomegaly / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003240:Connective Tissue Diseases / Q000503:physiopathology; D051765:Early Growth Response Transcription Factors / Q000502:physiology*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051785:Smad Proteins / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology
D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D051785:Smad Proteins; D016212:Transforming Growth Factor beta